| |
Records |
Links |
|
Author |
Aviad, A.D.; Houpt, J.B. |
|
| |
Title |
The molecular weight of therapeutic hyaluronan (sodium hyaluronate): how significant is it? |
Type |
Journal Article |
| |
Year |
1994 |
Publication |
The Journal of rheumatology |
Abbreviated Journal |
J Rheumatol |
|
| |
Volume |
21 |
Issue |
2 |
Pages |
297-301 |
|
| |
Keywords |
Animals; Horse Diseases/drug therapy; Horses; Humans; Hyaluronic Acid/*chemistry/*therapeutic use; Joint Diseases/*drug therapy/veterinary; Molecular Weight; Osteoarthritis/drug therapy/veterinary; Synovial Fluid/drug effects/physiology; Viscosity |
|
| |
Abstract |
Various molecular weight hyaluronic acid (HA) preparations have been injected into joints for the treatment of human and equine osteoarthritis. A therapeutic advantage has been claimed for commercial products with a molecular weight in the range found in normal synovial fluid (SF), compared to lower molecular weight products. But a correlation between molecular weight and efficacy is not borne out by an analysis of the available literature on clinical results. SF viscosity, HA concentration, HA molecular weight and rate of synthesis in joint disease. It is proposed that the beneficial effect of injected HA in joint disease may be due to pharmacological rather than to physical properties. |
|
| |
Address |
Rheumatic Disease Unit, Mount Sinai Hospital, University of Toronto, ON, Canada |
|
| |
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 |
0315-162X |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:8182640 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
35 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Houpt, K.A.; Northrup, N.; Wheatley, T.; Houpt, T.R. |
|
| |
Title |
Thirst and salt appetite in horses treated with furosemide |
Type |
Journal Article |
| |
Year |
1991 |
Publication |
Journal of applied physiology (Bethesda, Md. : 1985) |
Abbreviated Journal |
J Appl Physiol |
|
| |
Volume |
71 |
Issue |
6 |
Pages |
2380-2386 |
|
| |
Keywords |
Animals; Appetite/*drug effects; Blood Volume; Diuresis; Drinking/drug effects; Female; Furosemide/*pharmacology; Horses; Natriuresis; Sodium, Dietary/*administration & dosage; Thirst/*drug effects |
|
| |
Abstract |
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) |
|
| |
Address |
Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401 |
|
| |
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 |
8750-7587 |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:1778936 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
38 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Sufit, E.; Houpt, K.A.; Sweeting, M. |
|
| |
Title |
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 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Hodgson, D.; Howe, S.; Jeffcott, L.; Reid, S.; Mellor, D.; Higgins, A. |
|
| |
Title |
Effect of prolonged use of altrenogest on behaviour in mares |
Type |
|
| |
Year |
2005 |
Publication |
Veterinary journal (London, England : 1997) |
Abbreviated Journal |
Vet J |
|
| |
Volume |
169 |
Issue |
1 |
Pages |
113-115 |
|
| |
Keywords |
Administration, Oral; Anabolic Agents/adverse effects/*pharmacology; Animals; Behavior, Animal/*drug effects; Body Constitution/drug effects; Body Weight/drug effects; *Doping in Sports; Female; Horses/*physiology; Social Behavior; Social Dominance; Time Factors; Trenbolone/adverse effects/*analogs & derivatives/*pharmacology |
|
| |
Abstract |
Erratum in:
Vet J. 2005 May;169(3):321.
Corrected and republished in:
Vet J. 2005 May;169(3):322-5.
Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. We concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares resulted in no effect on dominance hierarchies, body mass or condition score. |
|
| |
Address |
Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia. davidh@camden.usyd.edu.au |
|
| |
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 |
1090-0233 |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:15683772 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
671 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Brown, R.F.; Houpt, K.A.; Schryver, H.F. |
|
| |
Title |
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 |
| |
|
| |
|
Author |
Houpt, T.R.; Houpt, K.A. |
|
| |
Title |
Nitrogen conservation by ponies fed a low -protein ration |
Type |
Journal Article |
| |
Year |
1971 |
Publication |
American journal of veterinary research |
Abbreviated Journal |
Am J Vet Res |
|
| |
Volume |
32 |
Issue |
4 |
Pages |
579-588 |
|
| |
Keywords |
Administration, Oral; Amino Acids/biosynthesis; Animals; Anti-Infective Agents/pharmacology; Body Weight/drug effects; Dietary Proteins/*pharmacology; Horses/*metabolism; Nitrogen/*metabolism; Urea/administration & dosage/antagonists & inhibitors/metabolism; Water/metabolism |
|
| |
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 |
0002-9645 |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:5110116 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
62 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
|
| |
Title |
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 |
|
| Permanent link to this record |
| |
|
| |
|
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. |
|
| |
Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
| |
Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
|
| |
Volume |
82 |
Issue |
2 |
Pages |
374-380 |
|
| |
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 |
|
| |
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. |
|
| |
Address |
Laboratory of Metabolism, CCR, NCI, NIH, 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 |
1096-6080 |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:15456926 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
71 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Jeong, S.; Han, M.; Lee, H.; Kim, M.; Kim, J.; Nicol, C.J.; Kim, B.H.; Choi, J.H.; Nam, K.-H.; Oh, G.T.; Yoon, M. |
|
| |
Title |
Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice |
Type |
Journal Article |
| |
Year |
2004 |
Publication |
Metabolism: clinical and experimental |
Abbreviated Journal |
Metabolism |
|
| |
Volume |
53 |
Issue |
10 |
Pages |
1284-1289 |
|
| |
Keywords |
Adipose Tissue/*anatomy & histology/drug effects; Animals; Antilipemic Agents/*pharmacology; Body Composition/*drug effects; Body Weight/drug effects; Dietary Fats/*pharmacology; Eating/drug effects; Fatty Acids/metabolism; Female; Gene Expression Regulation/drug effects; Leptin/metabolism; Liver/metabolism; Mice; Mice, Inbred C57BL; Ovariectomy; Procetofen/*pharmacology; RNA, Messenger/biosynthesis/genetics; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism; Transcription Factors/biosynthesis/genetics/metabolism; Weight Gain/*drug effects |
|
| |
Abstract |
Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice. |
|
| |
Address |
Department of Life Sciences, Mokwon University, Taejon, Korea |
|
| |
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 |
0026-0495 |
ISBN |
|
Medium |
|
|
| |
Area |
|
Expedition |
|
Conference |
|
|
| |
Notes |
PMID:15375783 |
Approved |
no |
|
| |
Call Number |
refbase @ user @ |
Serial |
72 |
|
| Permanent link to this record |
| |
|
| |
|
Author |
Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
|
| |
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 |
| |
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 |
|
| Permanent link to this record |
