Home | << 1 2 3 4 5 6 7 >> |
Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum, L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res, 64(11), 3849–3854.
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.
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
|
McGreevy, P. D., Webster, A. J., & Nicol, C. J. (2001). Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses. Vet. Rec., 148(19), 592–596.
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.
|
Spadavecchia, C., Arendt-Nielsen, L., Spadavecchia, L., Mosing, M., Auer, U., & van den Hoven, R. (2007). Effects of butorphanol on the withdrawal reflex using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. Vet Anaesth Analg, 34(1), 48–58.
Abstract: OBJECTIVE: To assess the effects of a single intravenous dose of butorphanol (0.1 mg kg(-1)) on the nociceptive withdrawal reflex (NWR) using threshold, suprathreshold and repeated subthreshold electrical stimuli in conscious horses. STUDY DESIGN: 'Unblinded', prospective experimental study. ANIMALS: Ten adult horses, five geldings and five mares, mean body mass 517 kg (range 487-569 kg). METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the palmar digital nerve. Repeated stimulations were applied to evoke temporal summation. Surface electromyography was performed to record and quantify the responses of the common digital extensor muscle to stimulation and behavioural reactions were scored. Before butorphanol administration and at fixed time points up to 2 hours after injection, baseline threshold intensities for NWR and temporal summation were defined and single suprathreshold stimulations applied. Friedman repeated-measures analysis of variance on ranks and Wilcoxon signed-rank test were used with the Student-Newman-Keul's method applied post-hoc. The level of significance (alpha) was set at 0.05. RESULTS: Butorphanol did not modify either the thresholds for NWR and temporal summation or the reaction scores, but the difference between suprathreshold and threshold reflex amplitudes was reduced when single stimulation was applied. Upon repeated stimulation after butorphanol administration, a significant decrease in the relative amplitude was calculated for both the 30-80 and the 80-200 millisecond intervals after each stimulus, and for the whole post-stimulation interval in the right thoracic limb. In the left thoracic limb a decrease in the relative amplitude was found only in the 30-80 millisecond epoch. CONCLUSION: Butorphanol at 0.1 mg kg(-1) has no direct action on spinal Adelta nociceptive activity but may have some supraspinal effects that reduce the gain of the nociceptive system. CLINICAL RELEVANCE: Butorphanol has minimal effect on sharp immediate Adelta-mediated pain but may alter spinal processing and decrease the delayed sensations of pain.
|
Doherty, T. J., & Frazier, D. L. (1998). Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies. Equine Vet J, 30(4), 300–303.
Abstract: This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively). The halothane MAC was redetermined after a 60 min infusion of lidocaine or saline. The baseline halothane MAC for the control group was mean +/- s.d. 0.94 +/- 0.03%, and no significant decrease occurred following saline infusion. Lidocaine decreased halothane MAC in a dose-dependent fashion (r = 0.86; P < 0.0003). The results indicate that i.v. lidocaine may have a role in equine anaesthesia.
Keywords: Anesthetics/administration & dosage/blood/*pharmacology; Anesthetics, Inhalation/administration & dosage/*analysis; Animals; Consciousness/drug effects; Dose-Response Relationship, Drug; Halothane/administration & dosage/*analysis; Horses/*physiology; Infusions, Intravenous/veterinary; Lidocaine/administration & dosage/blood/*pharmacology; Male
|
Carroll, G. L., Matthews, N. S., Hartsfield, S. M., Slater, M. R., Champney, T. H., & Erickson, S. W. (1997). The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies. Vet Surg, 26(1), 69–77.
Abstract: Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered.
Keywords: Adrenergic alpha-Antagonists/administration & dosage/*pharmacology; Animals; Behavior, Animal/drug effects/physiology; Blood Glucose/metabolism; Blood Pressure/drug effects/physiology; Consciousness/physiology; Dose-Response Relationship, Drug; Drug Interactions; Epinephrine/blood; Fatty Acids, Nonesterified/blood; Female; Heart Rate/drug effects/physiology; Horse Diseases/metabolism/physiopathology/psychology; Horses/blood/metabolism/*physiology; Hydrocortisone/blood; Hypnotics and Sedatives/administration & dosage/*pharmacology; Imidazoles/administration & dosage/*pharmacology; Injections, Intravenous; Male; Norepinephrine/blood; Receptors, Adrenergic, alpha/drug effects/*physiology; Stress/metabolism/physiopathology/veterinary; Time Factors; Tolazoline/administration & dosage/*pharmacology
|
Grubb, T. L., Foreman, J. H., Benson, G. J., Thurmon, J. C., Tranquilli, W. J., Constable, P. D., et al. (1996). Hemodynamic effects of calcium gluconate administered to conscious horses. J Vet Intern Med, 10(6), 401–404.
Abstract: Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.
Keywords: Animals; Blood Pressure/drug effects/physiology; Calcium/blood; Calcium Gluconate/administration & dosage/*pharmacology; Cardiac Output/drug effects/physiology; Consciousness/*physiology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Hemodynamic Processes/*drug effects/physiology; Horses/blood/*physiology; Infusions, Intravenous; Male; Myocardial Contraction/drug effects/physiology; Respiration/drug effects/physiology; Stroke Volume/drug effects/physiology; Time Factors
|
Trim, C. M., Moore, J. N., & Clark, E. S. (1989). Renal effects of dopamine infusion in conscious horses. Equine Vet J Suppl, (7), 124–128.
Abstract: An ultrasonic flow probe was implanted around a branch of the left renal artery in five horses. The effects of dopamine were studied in the unsedated horses 10 days after surgery. Three experiments, separated by at least two days, were performed in random order on each horse. In two experiments, dopamine was infused intravenously for 60 mins at either 2.5 and 5.0 micrograms/kg bodyweight (bwt)/min. Saline was infused for 60 mins before and after each infusion, and for 180 mins in the third experiment as a control. Renal blood flow increased during administration of dopamine at both dose rates (P = 0.0001). Urine volume increased (P = 0.055), and osmolality decreased (P < 0.05), with infusion of dopamine at 5.0 micrograms/kg bwt/min. Arterial blood pressure and heart rate were not significantly affected. Fractional excretions of sodium and potassium were not significantly changed with dopamine infusion. The higher dopamine dose rate was accompanied by dysrhythmias in some horses.
Keywords: Animals; Blood Pressure/drug effects/physiology; Consciousness/*physiology; Creatinine/blood; Dopamine/administration & dosage/*pharmacology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Horses/*physiology; Infusions, Intravenous/veterinary; Kidney/blood supply/*drug effects/physiology; Osmolar Concentration; Potassium/blood; Random Allocation; Regional Blood Flow/drug effects/physiology; Renal Artery/drug effects/physiology/ultrasonography; Sodium/blood; Time Factors; Ultrasonography/methods/veterinary; Urination/physiology
|
Lees, P., & Tavernor, W. D. (1970). Influence of halothane and catecholamines on heart rate and rhythm in the horse. Br J Pharmacol, 39(1), 149–159.
Keywords: Anesthesia, Inhalation; Animals; Arrhythmia/*chemically induced; Atropine/pharmacology; Catecholamines/*pharmacology; Consciousness; Epinephrine/administration & dosage; Ethers; Female; Halothane/*pharmacology; Heart Rate/*drug effects; Horses; Hypercapnia/physiopathology; Isoproterenol/pharmacology; Male; Norepinephrine/pharmacology; Propranolol/pharmacology
|
Tavernor, W. D., & Lees, P. (1968). A pharmacological investigation of the influence of suxamethonium on cardiac function in the horse. Experientia, 24(6), 582–583.
Keywords: 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
|
Alexander, F. (1978). The effect of some anti-diarrhoeal drugs on intestinal transit and faecal excretion of water and electrolytes in the horse. Equine Vet J, 10(4), 229–234.
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.
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
|