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Author Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S.
Title (up) 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
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3565 ISBN Medium
Area Expedition Conference
Notes PMID:15356214 Approved no
Call Number refbase @ user @ Serial 73
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Author Madigan, J.E.; Kortz, G.; Murphy, C.; Rodger, L.
Title (up) Photic headshaking in the horse: 7 cases Type Journal Article
Year 1995 Publication Equine Veterinary Journal Abbreviated Journal Equine Vet J
Volume 27 Issue 4 Pages 306-311
Keywords Animals; Anti-Allergic Agents/therapeutic use; *Behavior, Animal; Cyproheptadine/therapeutic use; Female; *Head; Horse Diseases/drug therapy/*etiology; Horses; Light/*adverse effects; Male; Movement Disorders/drug therapy/etiology/*veterinary
Abstract Seven horses with headshaking are described. No physical abnormalities were detected in any of the cases. Six of these horses had onset of clinical signs in the spring. The role of light was assessed by application of a blindfold or dark grey lens to the eyes, covering the eyes with a face mask and observing the horse in total darkness outdoors. Cessation of headshaking was observed with blindfolding (5/5 horses), night darkness outdoors (4/4 horses) and use of grey lenses (2/3 horses). Outdoor behaviour suggested efforts to avoid light in 4/4 cases. The photic sneeze in man is suggested as a putative mechanism for equine headshaking. Five of 7 horses had improvement with cyproheptadine treatment (0.3 mg/kg bwt b.i.d.). Headshaking developed within 2 calendar weeks of the same date for 3 consecutive years in one horse. Neuropharmacological alterations associated with photoperiod mechanisms leading to optic trigeminal summation are suggested as possible reasons for spring onset of headshaking.
Address Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis 95616-8737, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0425-1644 ISBN Medium
Area Expedition Conference
Notes PMID:8536668 Approved no
Call Number refbase @ user @ Serial 1940
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Author Sufit, E.; Houpt, K.A.; Sweeting, M.
Title (up) Physiological stimuli of thirst and drinking patterns in ponies Type Journal Article
Year 1985 Publication Equine veterinary journal Abbreviated Journal Equine Vet J
Volume 17 Issue 1 Pages 12-16
Keywords Animals; Blood Proteins/analysis; Drinking Behavior/drug effects/*physiology; Furosemide/pharmacology; Horses/*physiology; Male; Osmolar Concentration; Osmotic Pressure; Sodium Chloride/pharmacology; Thirst/drug effects/*physiology; Time Factors; Water Deprivation/physiology
Abstract The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivation period. In order to determine if an increase in plasma osmolality would stimulate thirst, 250 ml of 15 per cent sodium chloride was infused intravenously. The ponies drank when osmolality increased 3 per cent and when plasma sodium rose from 136 +/- 3 mmol/litre to 143 +/- 3 mmol/litre. Ponies infused with 15 per cent sodium chloride drank 2.9 +/- 0.7 kg; those infused with 0.9 per cent sodium chloride drank 0.7 +/- 0.5 kg. In order to determine if a decrease in plasma volume would stimulate thirst, ponies were injected with 1 or 2 mg/kg bodyweight (bwt) frusemide. Plasma protein rose from 68 +/- 2 g/litre pre-injection to 75 +/- 2 g/litre 1 h after 1 mg/kg bwt frusemide and to 81 +/- 1 g/litre 1 h after 2 mg/kg bwt frusemide.(ABSTRACT TRUNCATED AT 250 WORDS)
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0425-1644 ISBN Medium
Area Expedition Conference
Notes PMID:3979367 Approved no
Call Number refbase @ user @ Serial 56
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Author Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J.
Title (up) PPARgamma in endothelial cells influences high fat diet-induced hypertension Type Journal Article
Year 2005 Publication American journal of hypertension : journal of the American Society of Hypertension Abbreviated Journal Am J Hypertens
Volume 18 Issue 4 Pt 1 Pages 549-556
Keywords Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology
Abstract BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.
Address Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0895-7061 ISBN Medium
Area Expedition Conference
Notes PMID:15831367 Approved no
Call Number refbase @ user @ Serial 69
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Author Blokland, A.
Title (up) Reaction time responding in rats Type Journal Article
Year 1998 Publication Neuroscience and Biobehavioral Reviews Abbreviated Journal Neurosci Biobehav Rev
Volume 22 Issue 6 Pages 847-864
Keywords Amphetamine/pharmacology; Animals; Behavior, Animal/drug effects/*physiology; Conditioning, Operant/drug effects/*physiology; Dopamine Uptake Inhibitors/pharmacology; Dose-Response Relationship, Drug; Male; Rats; Rats, Inbred Lew; Reaction Time/drug effects/*physiology
Abstract The use of reaction time has a great tradition in the field of human information processing research. In animal research the use of reaction time test paradigms is mainly limited to two research fields: the role of the striatum in movement initiation; and aging. It was discussed that reaction time responding can be regarded as “single behavior”, this term was used to indicate that only one behavioral category is measured, allowing a better analysis of brain-behavior relationships. Reaction time studies investigating the role of the striatum in motor functions revealed that the initiation of a behavioral response is dependent on the interaction of different neurotransmitters (viz. dopamine, glutamate, GABA). Studies in which lesions were made in different brain structures suggested that motor initiation is dependent on defined brain structures (e.g. medialldorsal striatum, prefrontal cortex). It was concluded that the use of reaction time measures can indeed be a powerful tool in studying brain-behavior relationships. However, there are some methodological constraints with respect to the assessment of reaction time in rats, as was tried to exemplify by the experiments described in the present paper. On the one hand one should try to control for behavioral characteristics of rats that may affect the validity of the parameter reaction time. On the other hand, the mean value of reaction time should be in the range of what has been reported in man. Although these criteria were not always met in several studies, it was concluded that reaction time can be validly assessed in rats. Finally, it was discussed that the use of reaction time may go beyond studies that investigate the role of the basal ganglia in motor output. Since response latency is a direct measure of information processing this parameter may provide insight into basic elements of cognition. Based on the significance of reaction times in human studies the use of this dependent variable in rats may provide a fruitful approach in studying brain-behavior relationships in cognitive functions.
Address Department of Psychology, University of Maastricht, The Netherlands
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0149-7634 ISBN Medium
Area Expedition Conference
Notes PMID:9809315 Approved no
Call Number Equine Behaviour @ team @ Serial 2807
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Author Trim, C.M.; Moore, J.N.; Clark, E.S.
Title (up) Renal effects of dopamine infusion in conscious horses Type Journal Article
Year 1989 Publication Equine veterinary journal. Supplement Abbreviated Journal Equine Vet J Suppl
Volume Issue 7 Pages 124-128
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
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.
Address Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602, USA
Corporate Author Thesis
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN ISBN Medium
Area Expedition Conference
Notes PMID:9118094 Approved no
Call Number refbase @ user @ Serial 99
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Author Dunn, M.F.; Branlant, G.
Title (up) Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation Type Journal Article
Year 1975 Publication Biochemistry Abbreviated Journal Biochemistry
Volume 14 Issue 14 Pages 3176-3182
Keywords *Alcohol Oxidoreductases/metabolism; Aldehydes/*pharmacology; Animals; Binding Sites; Enzyme Activation/drug effects; Horses; Hydrogen-Ion Concentration; Kinetics; Liver/enzymology; *NAD/analogs & derivatives/pharmacology; Oxidation-Reduction; Protein Binding; Spectrophotometry; Spectrophotometry, Ultraviolet; Temperature; *Zinc/pharmacology
Abstract 1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step.
Address
Corporate Author Thesis
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Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0006-2960 ISBN Medium
Area Expedition Conference
Notes PMID:238585 Approved no
Call Number Equine Behaviour @ team @ Serial 3817
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Author Pennisi, E.
Title (up) Schizophrenia clues from monkeys Type
Year 1997 Publication Science (New York, N.Y.) Abbreviated Journal Science
Volume 277 Issue 5328 Pages 900
Keywords 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
Abstract
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0036-8075 ISBN Medium
Area Expedition Conference
Notes PMID:9281070 Approved no
Call Number Equine Behaviour @ team @ Serial 2844
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Author Domjan, M.
Title (up) Selective suppression of drinking during a limited period following aversive drug treatment in rats Type Journal Article
Year 1977 Publication Journal of Experimental Psychology. Animal Behavior Processes Abbreviated Journal J Exp Psychol Anim Behav Process
Volume 3 Issue 1 Pages 66-76
Keywords Animals; *Avoidance Learning; Awareness; Conditioning, Operant; Dose-Response Relationship, Drug; Drinking Behavior/*drug effects; Lithium/*poisoning; Male; Osmolar Concentration; Rats; Saccharin/administration & dosage; *Taste; Time Factors
Abstract Administration of lithium chloride disrupted the intake of flavored solutions but not water in rats. This intake suppression was directly related to the amount of lithium administered (Experiment 1), occurred with both palatable and unpalatable novel saccharin solutions (Experiment 2), but was only observed if subjects were tested starting less than 75 min. after lithium treatment (Experiment 3). Twenty-five daily exposures to saccharin did not attenuate the effect (Experiment 4). However, in saccharin-reared and vinegar-reared rats, lithium did not disrupt consumption of the solutions these subjects had access to throughout life, even though suppressions of intake were observed when these subjects were tested with novel flavors (Experiment 5). The selective disruption of drinking is interpreted as a novelty-dependent sensitization reaction to the discomfort of aversive drug administration.
Address
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Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0097-7403 ISBN Medium
Area Expedition Conference
Notes PMID:845544 Approved no
Call Number Equine Behaviour @ team @ Serial 2788
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Author Brown, R.F.; Houpt, K.A.; Schryver, H.F.
Title (up) Stimulation of food intake in horses by diazepam and promazine Type Journal Article
Year 1976 Publication Pharmacology, biochemistry, and behavior Abbreviated Journal Pharmacol Biochem Behav
Volume 5 Issue 4 Pages 495-497
Keywords Age Factors; Animals; Diazepam/*pharmacology; Diet; Feeding Behavior/*drug effects; Female; Horses/*physiology; Male; Promazine/*pharmacology; Stimulation, Chemical
Abstract In two adult horses doses of 0.02-0.03 mg/kg diazepam, intravenously, increased 1 hr intake 54-75% above control levels. Intake was stimulated when the diet was a high grain, calorically dense one and also when the diet was a high fiber, calorically dilute one. Two young rapidly growing weanling horses showed an even more pronounced stimulation of intake. Following diazepam 1 hr intake was increased 105-240% above control lelvels. Promazine at a dose of 0.5 mg/kg also stimulated intake in adult horses, but not as markedly as did diazepam. A transquilizer and a neuroleptic appear to have a stimulatory eff upon short-term intake in horses.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0091-3057 ISBN Medium
Area Expedition Conference
Notes PMID:1005496 Approved no
Call Number refbase @ user @ Serial 60
Permanent link to this record