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Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation.

Koerts-de Lang E, Hesselink MK, Drost MR, van der Vusse GJ, Wouters EF, Schols AM.

Department of Pulmonology, Nutrition Toxicology and Environment Research Institute Maastricht, University Hospital Maastricht, The Netherlands.

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl beta-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25 mg x kg(-1) x day(-1) for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31 mg x kg(-1) x day(-1) for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P < 0.01), glycogen synthase [GS(i + d)] activity (P < 0.05) and glycogen content (P < 0.01) in the tibialis anterior muscle. The PR and ND caused no alterations in PFK or citrate synthase (CS) activity compared to FF. Compared to PR, TR induced an increase in PFK (P < 0.01), CS (P < 0.05) and GS(i + d) activity (P < 0.01). Both TR and PR caused an increased muscle glycogen content, being more pronounced in TR (P < 0.05). Compared to ND, TR induced an increased CS (P < 0.05) and GS(i + d) activity (P < 0.01) and glycogen content (P < 0.01). The ND resulted in a decreased glycogen content compared to FF (P < 0.05). None of the treatments affected the activity of glycogen phosphorylase, beta-hydroxyacyl coenzyme A dehydrogenase and lactate dehydrogenase. It was concluded that corticosteroids led to an increased muscle glycogen content; however, the changes in the enzymes of carbohydrate metabolism were corticosteroid type specific and did not relate to undernutrition, which accompanied the triamcinolone treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10048633&dopt=Abstract triamcinolone Kenalog



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Placental glucose transporter expression is regulated by glucocorticoids.

Hahn T, Barth S, Graf R, Engelmann M, Beslagic D, Reul JM, Holsboer F, Dohr G, Desoye G.

Institute of Histology and Embryology, University of Graz, Austria. tom.hahn kfunigraz.ac.at

Although glucocorticoids play important roles in development and fetal programming, they are widely used for treatment of a variety of diseases during pregnancy. In various tissues, glucocorticoids down-regulate glucose transport systems; however, their effects on glucose transporters in the placenta are unknown. In the present study, the glucose carrier proteins GLUT1 and GLUT3 were localized in the trophoblast and endothelium of the human, rat, and mouse placenta. Subsequently, it was investigated whether glucocorticoids affect messenger ribonucleic acid and protein expression of these molecules by Northern and Western blotting using 1) human term placental trophoblast cells cultured in the presence or absence of 0.5, 5, and 50 micromol/L triamcinolone; 2) placentas of rats that received a single i.p. dose of 0.38 mg/kg triamcinolone; and 3) placentas of transgenic mice bearing an antisense glucocorticoid receptor gene construct. In all of these systems, both glucose transporters were significantly down-regulated (P < 0.05), with the exception of increased GLUT3 messenger ribonucleic acid and protein levels in transgenic mice. The results demonstrate that triamcinolone is a potent regulator of placental GLUT1 and GLUT3 expression involving the glucocorticoid receptor. We speculate that impaired expression of placental glucose transporters after glucocorticoid administration might contribute to the adverse side-effects, the foremost of which is a growth-retarded fetus, of this treatment during pregnancy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10199793&dopt=Abstract triamcinolone Kenalog



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Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures.

Kochhar R, Ray JD, Sriram PV, Kumar S, Singh K.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

BACKGROUND: Intralesional corticosteroid injection has been shown to be effective in refractory esophageal strictures of various etiologies. The present study was conducted to determine the efficacy of intralesional triamcinolone in augmenting results of endoscopic dilation in corrosive esophageal strictures. METHODS: Seventeen patients with corrosive esophageal strictures were treated with endoscopic dilation together with injection of triamcinolone acetonide into the stricture. Fourteen patients were already undergoing dilation; 3 patients were newly recruited. The interval between dilations and frequency of dilation were calculated before and after corticosteroid injections, and periodic dilation index was calculated as number of dilations/number of months. RESULTS: The mean age of the 17 patients (8 men and 9 women) was 30+/-9.21 (range 13 to 52). Thirteen had strictures due to acid ingestion, four to alkali ingestion. There were 18 strictures in total, involving the upper (n = 2), middle (n = 10), and lower (n = 6) thirds of esophagus. Fourteen patients already on a dilation program had undergone 27.92+/-28.63 (range 6 to 92) dilations over a period of 22.92+/-30.73 months (range 2 to 96) before corticosteroid injections. Nine patients received a single injection of triamcinolone, whereas four each had two and three sessions. The dilation requirement after injections in these 14 patients was reduced to 3.57+/-2.90 (range 0 to 10) dilations over a period of 10.5+/-5.58 (range 4 to 21) months. The median total periodic dilation index irrespective of corticosteroid therapy was 0.33 (range 0.55 to 1.8). In 12 of the 14 patients, periodic dilation index before injections (range 0.91 to 3.0, median 1.67) was higher than the median total periodic dilation index and in all the 14 patients periodic dilation index after corticosteroid therapy (range 0 to 0.83, median 0.32) was less than the median of total periodic dilation index (p < 0.01). In addition three patients received intralesional corticosteroid injections at the time of first dilation. These three patients could be effectively dilated with 5, 3, and 3 dilations. CONCLUSIONS: Intralesional triamcinolone injections augment the effects of endoscopic dilation in patients with corrosive esophageal strictures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10202068&dopt=Abstract triamcinolone Kenalog



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Effects of five commonly used glucocorticoids on haemangioma in vitro.

Hasan Q, Tan ST, Xu B, Davis PF.

Centre for the Study and Treatment of Vascular Birthmarks, Maxillofacial and Burns Unit, Hutt Hospital, Reconstructive Plastic Surgery Research Institute of New Zealand, Wellington, New Zealand.

1. High-dose systemic or intralesional steroids are the first-line pharmacological treatments for haemangioma. However, the mechanism of action of steroids is unknown. Using the in vitro model developed by us, the present study examined some of the effects of five commonly used glucocorticoids on haemangioma biopsies taken from two patients. 2. At 12 micro mol/L, triamcinolone and dexamethasone consistently exhibited capillary growth inhibition, whereas methylprednisolone displayed an inhibitory effect during the first 7 days of culture. At this concentration, inhibition of capillary growth was observed in betamethasone-treated cultures derived from one patient but not in those derived from the other. However, hydrocortisone had a negligible effect on capillary growth. 3. Transcription of various factors considered important for haemangioma development were studied by reverse transcription-polymerase chain reaction. Neither vascular endothelial growth factor nor fibroblast growth factor-2 played a vital role in steroid-induced inhibition of capillary growth. All glucocorticoids induced a marked decrease of interleukin (IL)-6 transcripts. 4. Capillary growth inhibition in cultures treated with all glucocorticoids, except triamcinolone, was associated with an increased transcription of clusterin/apolipoprotein J (clust/apoJ), an apoptotic gene. There was increased transcription of mitochondrial cytochrome (cyt) b in the inhibited cultures resulting from triamcinolone, dexamethasone or methylprednisolone treatment that was associated with capillary growth inhibition, suggesting an important role of mitochondria in glucocorticoid-induced regression of haemangioma. 5. Our results indicate that glucocorticoids may modulate haemangiogenesis via an upregulation of cyt b, clust/apoJ and/or IL-6. The variable effects of different glucocorticoids on one or more of these factors may explain the interindividual variation in the in vivo response of haemangioma to the steroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12603341&dopt=Abstract triamcinolone Kenalog



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Dose-dependent effects of corticosteroids on the expression of matrix-related genes in normal and cytokine-treated articular chondrocytes.

Richardson DW, Dodge GR.

Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348-1692, USA. dwr vet.upenn.edu

OBJECTIVE AND DESIGN: To assess the effects of glucocorticoids on the expression of multiple matrix-related genes in normal and cytokine-treated cultured equine articular chondrocytes in a phenotypically correct suspension culture. MATERIAL OR SUBJECTS: Articular cartilage harvested from the joints of 15 foals, 7 yearling horses, and 16 adult horses. Treatment: Glucocorticoids (dexamethasone, prednisolone, triamcinolone) at 10(-10) to 10(-4) M. METHODS: Equine articular chondrocytes maintained in suspension cultures were treated with glucocorticoids with and without human recombinant interleukin 1-beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha). Northern blots of total RNA from the treated cells were probed with equine specific cDNA probes for a number of cartilage matrix-related genes. Zymography, Western blotting, and fluorography were also performed to study the effects on protein synthesis. RESULTS: The glucocorticoids, dexamethasone, triamcinolone, and prednisolone, markedly decreased MMP1, MMP3, MMP13, TIMPI, and ferritin steady-state mRNA levels. There were no qualitative differences seen among the tested corticosteroids although dexamethasone and triamcinolone appeared to be slightly more potent than prednisolone. The effects of the glucocorticoids on MMP transcription occurred consistently at lower doses than those required to similarly downregulate type II collagen and aggrecan. Link protein and fibronectin mRNA were increased by the glucocorticoids, and biglycan and decorin were minimally affected. Fluorography of [14-C] proline-labeled media demonstrated that the decrease in type II collagen transcription (mRNA levels) was paralleled at the protein level. Zymography and Western blotting confirmed the decrease in functional metalloproteinases found in chondrocyte cultures following glucocorticoid treatment. CONCLUSIONS: The effects of glucocorticoids are complex inasmuch as they differentially affect numerous genes involved in the composition of cartilage matrix and the degradation of that matrix. This study provides new insight into the effects of glucocorticoids on the regulation of extra-cellular matrix and matrix-related genes by demonstrating that low doses of glucocorticoids can inhibit the degradative metalloproteinases with minimal negative effects on the transcription of extracellular matrix genes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12608648&dopt=Abstract triamcinolone Kenalog



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Effects of topical corticosteroids on inflammatory mediator-induced eicosanoid release by human airway epithelial cells.

Aksoy MO, Li X, Borenstein M, Yi Y, Kelsen SG.

Pulmonary Division, Department of Medicine, Temple University School of Medicine, Philadelphia, USA.

BACKGROUND: Airway epithelial cells are among the first cells to come in contact with aerosolized corticosteroids. However, the relative potencies and time course of action of the several commonly used aerosolized corticosteroids on eicosanoid production by airway epithelial cells are unknown. OBJECTIVES: This study compared the effects of fluticasone, budesonide, and triamcinolone on eicosanoid output by human airway epithelial cells in vitro. We also determined the spectrum of eicosanoids affected and the mechanism for corticosteroid action. METHODS: Cultured BEAS-2B airway epithelial cells (a transformed cell line) were exposed to corticosteroids (1 nmol/L to 1 micromol/L) for 2 to 48 hours and then assayed for basal- and bradykinin (BK)-stimulated eicosanoid output. The eicosanoid profile was identified by HPLC in tritiated arachidonic acid prelabelled cells, and PGE2, the major eicosanoid product, was quantitated by RIA. The effect of corticosteroids on the immunoreactivity of key proteins involved in eicosanoid metabolism (ie, cyclooxygenase [COX], phospholipase A2 [PLA2], and Clara cell protein, a PLA2 inhibitor) was determined by Western blotting. RESULTS: Eicosanoid output was largely confined to prostaglandins with values of 5 +/- 2 and 82 +/- 35 ng PGE2/10(6) cells for basal- and BK stimulation, respectively (n = 8). All 3 corticosteroids inhibited basal- and BK-induced PGE2 output in a dose- and time-dependent manner. Fluticasone and budesonide completely eliminated PGE2 output in nanomolar concentrations in contrast to triamcinolone, which required micromolar concentration. The rank order of potency was: fluticasone = budesonide > triamcinolone. The time course of action for PGE2 inhibition also differed, with budesonide acting more slowly than the other 2 corticosteroids (P = .04). All 3 corticosteroids markedly reduced COX2 with little effect on COX1, cPLA2 (Type IV), or iPLA2 (Type VI) immunoreactivity or their relative distribution in cytosol versus membrane fractions. Clara cell protein immunoreactivity was undetectable in control and corticosteroid-treated cell lysates. CONCLUSION: These results show that in a human airway epithelial cell line, the 3 inhaled corticosteroids commonly used to treat asthma differ in onsets of action as inhibitors of prostaglandin synthesis and vary considerably in potency. All 3 corticosteroids act mechanistically in similar fashion by inhibiting COX2 synthesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10359890&dopt=Abstract triamcinolone Kenalog