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Author |
Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. |
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Title |
Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha |
Type |
Journal Article |
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Year |
2004 |
Publication |
Cancer research |
Abbreviated Journal |
Cancer Res |
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Volume |
64 |
Issue |
11 |
Pages |
3849-3854 |
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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 |
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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. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0008-5472 |
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PMID:15172993 |
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Call Number |
refbase @ user @ |
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74 |
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Author |
Alexander, F. |
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Title |
The effect of some anti-diarrhoeal drugs on intestinal transit and faecal excretion of water and electrolytes in the horse |
Type |
Journal Article |
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Year |
1978 |
Publication |
Equine veterinary journal |
Abbreviated Journal |
Equine Vet J |
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Volume |
10 |
Issue |
4 |
Pages |
229-234 |
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Keywords |
Animals; Antidiarrheals/*pharmacology; Atropine/pharmacology; Electrolytes/*analysis/urine; Feces/*analysis; Gastrointestinal Motility/*drug effects; Horses/*metabolism/physiology; Loperamide/pharmacology; Male; Meperidine/pharmacology; Morphine/pharmacology; Opium/pharmacology; Water/*analysis |
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Abstract |
The effect of morphine, Tinct. opii, loperamide, pethidine and atropine on intestinal transit and the faecal and urinary excretion of water and electrolytes was studied in ponies. The rate of passage of a particulate marker was slowed by morphine, hastened then slowed by loperamide and Tinct. opii, and hastened by atropine. The liquid marker was slowed by Tinct. opii and hastened then slowed by the other drugs. Only loperamide decreased the faecal sodium excretion. This drug also decreased faecal water and weight; it appeared worthy of clinical trial in diarrhoea. Tinct. opii decreased by morphine, pethidine and atropine increased faecal water. |
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0425-1644 |
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PMID:738263 |
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Call Number |
refbase @ user @ |
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110 |
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Pennisi, E. |
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Title |
Schizophrenia clues from monkeys |
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1997 |
Publication |
Science (New York, N.Y.) |
Abbreviated Journal |
Science |
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277 |
Issue |
5328 |
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900 |
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Animals; Antipsychotic Agents/pharmacology; Behavior, Animal/drug effects; *Cercopithecus aethiops; Clozapine/pharmacology; Cognition/drug effects; *Disease Models, Animal; Dopamine/*metabolism; Excitatory Amino Acid Antagonists/pharmacology; Memory/drug effects; Phencyclidine/*pharmacology; Prefrontal Cortex/*metabolism; Schizophrenia/chemically induced/drug therapy/*metabolism; Schizophrenic Psychology |
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0036-8075 |
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PMID:9281070 |
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Equine Behaviour @ team @ |
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2844 |
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Author |
Houpt, K.A.; Northrup, N.; Wheatley, T.; Houpt, T.R. |
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Title |
Thirst and salt appetite in horses treated with furosemide |
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Journal Article |
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Year |
1991 |
Publication |
Journal of applied physiology (Bethesda, Md. : 1985) |
Abbreviated Journal |
J Appl Physiol |
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Volume |
71 |
Issue |
6 |
Pages |
2380-2386 |
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Keywords |
Animals; Appetite/*drug effects; Blood Volume; Diuresis; Drinking/drug effects; Female; Furosemide/*pharmacology; Horses; Natriuresis; Sodium, Dietary/*administration & dosage; Thirst/*drug effects |
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When a preliminary experiment in sodium-replete ponies revealed an increase, but not a significant increase, in salt consumption after furosemide treatment, the experiment was repeated using sodium-deficient horses in which aldosterone levels might be expected to be elevated to test the hypothesis that a background of aldosterone is necessary for salt appetite. Ten Standardbred mares were injected intravenously with furosemide or an equivalent volume of 0.9% sodium chloride as a control to test the effect of furosemide on their salt appetite and blood constituents. Sodium intake and sodium loss in urine, as well as water intake and urine output, were measured and compared to determine accuracy of compensation for natriuresis and diuresis. Plasma protein and packed cell volume showed significant increases in response to furosemide treatment (F = 29.31, P less than 0.001 and F = 11.20, P less than 0.001, respectively). There were no significant changes in plasma sodium concentration or osmolality in response to the treatment (P greater than 0.05). The furosemide-treated horses consumed 126 +/- 14.8 g salt, significantly more than when they were given the control injection (94.5 +/- 9.8 g; t = 2.22, P = 0.05). In response to furosemide, horses lost 962 +/- 79.7 and consumed 2,170 +/- 5 meq sodium; however, compared with control, they lost 955 meq more sodium and ingested only 570 meq more sodium, so they were undercompensating for natriuresis. The furosemide-treated horses drank 9.6 +/- 0.8 kg of water, significantly more than when they received the control injection (6.4 +/- 0.8 kg; t = 6.9, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) |
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Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401 |
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8750-7587 |
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Notes |
PMID:1778936 |
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no |
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Call Number |
refbase @ user @ |
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38 |
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Author |
Tavernor, W.D.; Lees, P. |
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A pharmacological investigation of the influence of suxamethonium on cardiac function in the horse |
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Journal Article |
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Year |
1968 |
Publication |
Experientia |
Abbreviated Journal |
Experientia |
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24 |
Issue |
6 |
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582-583 |
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Animals; Arrhythmia/chemically induced; Consciousness; Halothane; Heart/innervation; Heart Rate/*drug effects; Horses/*physiology; Oxygen; Propranolol/pharmacology; Receptors, Sensory/drug effects; Stimulation, Chemical; Succinylcholine/antagonists & inhibitors/*pharmacology; Sympathetic Nervous System/physiology; Tachycardia/chemically induced; Thiopental |
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0014-4754 |
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PMID:5697737 |
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refbase @ user @ |
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104 |
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Author |
Alexander, F. |
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A study of parotid salivation in the horse |
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Journal Article |
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Year |
1966 |
Publication |
The Journal of physiology |
Abbreviated Journal |
J Physiol |
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184 |
Issue |
3 |
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646-656 |
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Animals; Atropine/*pharmacology; Bicarbonates/metabolism; Calcium/metabolism; Chlorides/metabolism; Horses; Mastication/*physiology; Parotid Gland/*physiology; Pilocarpine/*pharmacology; Potassium/metabolism; Salivation/*drug effects; Sodium/metabolism; Tetracaine/*pharmacology |
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0022-3751 |
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PMID:5963737 |
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refbase @ user @ |
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119 |
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Hada, T.; Ohmura, H.; Mukai, K.; Eto, D.; Takahashi, T.; Hiraga, A. |
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Title |
Utilisation of the time constant calculated from heart rate recovery after exercise for evaluation of autonomic activity in horses |
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Journal Article |
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Year |
2006 |
Publication |
Equine Veterinary Journal. Supplement |
Abbreviated Journal |
Equine Vet J Suppl |
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Issue |
36 |
Pages |
141-145 |
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Keywords |
Animals; Atropine/pharmacology; Autonomic Nervous System/drug effects/*physiology; Exercise Test/veterinary; Female; Heart Rate/*physiology; Horses/*physiology; Male; Oxygen Consumption/*physiology; Parasympatholytics/*pharmacology; Physical Conditioning, Animal/*physiology; Physical Fitness/physiology; Propranolol/pharmacology |
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REASONS FOR PERFORMING STUDY: Heart rate (HR) recovery immediately after exercise is controlled by autonomic functions and the time constant (T) calculated from HR recovery is thought to be an index of parasympathetic activity in man. OBJECTIVES: To investigate whether it is possible to evaluate autonomic function using the time constant in horses. METHODS: Five Thoroughbred horses were subjected to a standard exercise test. Following pre-medication with saline, atropine and/or propranolol, the horses ran for 2.5 min at a speed of 8 m/sec at a 10% incline and T was calculated from HR after the exercise. Secondly, 7 Thoroughbred horses were then trained for 11 weeks and T and maximal oxygen uptake (VO2max) measured at intervals of 1 or 2 weeks. In 6 horses, T with atropine pre-medication was also measured before and after the whole training period. Furthermore, the HR variability at rest was evaluated by power spectral analysis at intervals of 3 or 4 weeks. RESULTS: Time constant was increased by atropine and/or propranolol pre-medication, decreased with the progress of training and inversely correlated with VO2max during training (r = 0.43, P<0.005). Parasympathetic blockade significantly decreased T only after and not before, the training; however, T was lower in post training than in pretraining, irrespective of parasympathetic blockade. On the other hand, parasympathetic activity at rest was attenuated and sympathetic activity became predominant following the training. CONCLUSION: Heart rate recovery is affected by sympathetic withdrawal and parasympathetic reactivation in horses and suggests that physical training hastened HR recovery by improving the parasympathetic function after exercise with aerobic capacity. However, the effects of other factors need to be considered because the training effect appeared on T even under parasympathetic blockade. The parasympathetic activity at rest is in contrast to that after exercise, suggesting that T does not reflect parasympathetic activity at rest. POTENTIAL RELEVANCE: If demonstrated how HR recovery is controlled after exercise, its analysis will be important in the evaluation of physical fitness in horses. |
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Equine Science Division, Hidaka Training and Research Center, Japan Racing Association, 535-13 Nischicha, Urakawa-cho, Uraakawagun, Hokkaido, Japan |
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PMID:17402409 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
4010 |
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Author |
Mitchell, D.; Kirschbaum, E.H.; Perry, R.L. |
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Title |
Effects of neophobia and habituation on the poison-induced avoidance of exteroceptive stimuli in the rat |
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Journal Article |
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Year |
1975 |
Publication |
Journal of Experimental Psychology. Animal Behavior Processes |
Abbreviated Journal |
J Exp Psychol Anim Behav Process |
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Volume |
1 |
Issue |
1 |
Pages |
47-55 |
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Animals; Avoidance Learning/*drug effects; *Awareness; *Cognition; Conditioning, Operant; Feeding Behavior/drug effects; *Habituation, Psychophysiologic; Injections, Intraperitoneal; Lithium/administration & dosage/poisoning; Male; Rats; *Taste; Time Factors; *Visual Perception |
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Two experiments on the role of neophobia in poison-induced aversions to exteroceptive stimuli are reported. In Experiment 1, rats were given either 10 or 25 days of habituation to the test situation prior to conditioning. Those animals with the longer habituation period avoided a complex of novel exteroceptive stimuli while those with the shorter habituation period did not. In Experiment 2 rats initially avoided the more novel of two containers, but gradually came to eat equal amounts from both. A single pairing of toxicosis with consumption from either the novel or the familiar container reinstated the avoidance of the novel container in both cases. The results were discussed in terms of an interaction between habituation and conditioning procedures. It was suggested that previously reported differences between interoceptive and exteroceptive conditioning effects may have been influenced by the differential novelty of the two classes of stimuli in the test situation. It was further suggested that non-contingently poisoned control groups should routinely be included in poison avoidance conditioning studies. |
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0097-7403 |
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PMID:1151289 |
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no |
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Equine Behaviour @ team @ |
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2791 |
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Author |
Yamazaki, Y.; Shinohara, N.; Watanabe, S. |
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Title |
Visual discrimination of normal and drug induced behavior in quails (Coturnix coturnix japonica) |
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Journal Article |
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Year |
2004 |
Publication |
Animal Cognition |
Abbreviated Journal |
Anim. Cogn. |
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Volume |
7 |
Issue |
2 |
Pages |
128-132 |
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Animals; Behavior, Animal/*drug effects; Classification; Coturnix/*physiology; *Discrimination Learning; *Generalization (Psychology); Ketamine/pharmacology; Male; Methamphetamine/pharmacology; *Pattern Recognition, Visual; Video Recording; Visual Perception |
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The ability to discriminate the physical states of others could be an adaptive behavior, especially for social animals. For example, the ability to discriminate illness behavior would be helpful for avoiding spoiled foods. We report on an experiment with Japanese quails testing whether these birds can discriminate the physical states of conspecifics. The quails were trained to discriminate between moving video images of quails injected with psychoactive drugs and those in a normal (not injected) condition. Methamphetamine (stimulant) or ketamine (anesthetic) were used to produce drug-induced behaviors in conspecifics. The former induced hyperactive behavior and the latter hypoactive behavior. The subject quails could learn the discrimination and showed generalization to novel images of the drug-induced behaviors. They did not, however, show discriminative behavior according to the type and dosage of the drugs. Thus, they categorized the behavior not on the basis of degree of activity, but on the basis of abnormality. |
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Biopsychologie, Institut fur Kognitive Neurowissenschaft, Fakultat fur Psychologie, Ruhr-Universitat Bochum, 44780 Bochum, Germany. yumyam@bio.psy.ruhr-uni-bochum.de |
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1435-9448 |
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PMID:15069613 |
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Equine Behaviour @ team @ |
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2527 |
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Author |
McGreevy, P.D.; Webster, A.J.; Nicol, C.J. |
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Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses |
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Journal Article |
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Year |
2001 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
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Volume |
148 |
Issue |
19 |
Pages |
592-596 |
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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 |
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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. |
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Department of Clinical Veterinary Science, University of Bristol, Langford |
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0042-4900 |
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PMID:11386445 |
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Call Number |
refbase @ user @ |
Serial |
86 |
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