Kenalog
Potentiation of glucocorticoid-induced cytolysis in sensitive human leukemic cells by an inhibitor of ADP-ribosylation.

Meyer AS, Schlechte JA, Schmidt TJ.

Department of Physiology and Biophysics, College of Medicine, University of Iowa, Iowa City 52242.

3-Aminobenzamide, a general inhibitor of poly(ADP-ribose)polymerase, potentiated the triamcinolone acetonide-mediated growth inhibition and lysis of the glucocorticoid-sensitive CEM-C7 human leukemic cell line. This potentiation was dose-dependent with maximal response being detected at 3 mM 3-aminobenzamide, and was completely blocked by the glucocorticoid receptor antagonist RU 38486. Scatchard analysis of whole cell specific [3H]triamcinolone acetonide binding data did not reveal any effect of 3-aminobenzamide on either the number of intracellular receptor binding sites or their affinity for the agonist. Treatment of the ICR-27 cell line, which is a glucocorticoid resistant mutant isolated from CEM-C7, with 3-aminobenzamide did not restore triamcinolone acetonide sensitivity. Similarly, 3-aminobenzamide treatment of several other lymphoid cell lines (human HL60 and IM-9 and murine L1210 cells) which contain functional receptors but are not normally lysed by glucocorticoid agonists, failed to induce sensitivity to triamcinolone acetonide. Since treatment of sensitive lymphoid cells with glucocorticoid agonists results in DNA fragmentation prior to cell death, these data suggest that 3-aminobenzamide potentiates the cytolytic response of sensitive cells to glucocorticoid agonists by inhibiting DNA excision repair mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2124310&dopt=Abstract triamcinolone Kenalog



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In vitro phototoxic properties of triamcinolone 16,17-acetonide and its main photoproducts.

Miolo G, Ricci A, Caffieri S, Levorato L, Fasani E, Albini A.

Department of Pharmaceutical Sciences, University of Padova, Padova, Italy. giorgia.miolo unipd.it

The phototoxicity of triamcinolone 16,17-acetonide has been estimated through a panel of in vitro tests. The main target involved in phototoxicity induced by triamcinolone appeared to be the cell membrane. Oxygen-independent photohemolysis was observed. A photochemical study in water and buffered solutions supported the conclusion that this is related to the action of radicals formed upon UV irradiation (in particular UV-B) by Norrish Type-I fragmentation of the C-20 ketone group. Peroxy radicals were formed in the presence of oxygen and were the active species in that case. Three photoproducts, isolated from the photodegradation of the drug, were submitted to the same toxicity tests. Two of them were proved to possess toxic or phototoxic properties on erythrocytes, primarily induced by UV-B light, and may participate in the photosensitizing activity of triamcinolone 16,17-acetonide. Our in vitro results suggest that the drug can elicit weak photosensitizing properties in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14653571&dopt=Abstract triamcinolone Kenalog



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Intravitreal triamcinolone does not alter basal vascular endothelial growth factor mRNA expression in rat retina.

Gao H, Qiao X, Gao R, Mieler WF, McPherson AR, Holz ER.

Department of Ophthalmology, Baylor College of Medicine, Cullen Eye Institute, 6560 Fannin, Suite 2200, Houston, TX 77030, USA. huagao55 hotmail.com

Intravitreal triamcinolone inhibits choroidal neovascularization. To investigate if vascular endothelial growth factor (VEGF) is affected, we examined VEGF expression after intravitreal triamcinolone administration in rat retina. Using in situ hybridization, we have found dense clustered VEGF mRNA signals in the retinal pigment epithelium, moderate patchy signals in the inner nuclear layer, and positive labeling in a sub-population of ganglion cells. Densitometry and northern blot analysis revealed no significant alteration of VEGF mRNA expression pattern and level 3-21 days after triamcinolone injection. Our data indicate that intravitreal triamcinolone does not affect basal VEGF mRNA expression in normal adult rat retina.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14659961&dopt=Abstract triamcinolone Kenalog



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Two-dimensional gel autoradiographic analyses of the effects of 1,25-dihydroxycholecalciferol on protein synthesis in clonal rat osteosarcoma cells.

Murray EJ, Murray SS, Manolagas SC.

Department of Medicine, University of California-San Diego, La Jolla.

The steady state synthesis of L-[35S]methionine-radiolabeled cellular proteins by two rat osteogenic sarcoma cell lines (G2 and C12) was examined by two-dimensional polyacrylamide gel electrophoresis under basal conditions and after 72-h treatments with 10 nM 1,25-dihydroxycholecalciferol or triamcinolone acetonide. Computer analysis resolved 681 spots, with mol wt ranging from 10-105K and isoelectric points ranging from 4.0-8.0. Fourteen spots were abundant (greater than or equal to 2000 parts/million), with the remainder occurring in limited abundance (150-2000 parts/million) in both clones. Only 28 proteins were radiolabeled at significantly different rates by G2 and C12 cells under basal conditions. The high degree of similarity in the identity and relative abundance of proteins synthesized by these distinct subclones suggests that minor changes in the levels of specific intracellular proteins may have major effects on the osteoblastic phenotype. 1,25-Dihydroxycholecalciferol [1,25-(OH)2D3] or triamcinolone acetonide treatment induced qualitative and quantitative changes in the synthesis of specific subsets of proteins, including induction of novel proteins, complete repression of proteins synthesized under basal conditions, and significant increases or decreases in the levels of others. 1,25-(OH)2D3 significantly altered the levels of 13 proteins in G2 cells and 28 proteins in C12 cells. 1,25-(OH)2D3 enhanced the synthesis of two proteins (no. 304 and 2506) in both subclones. The remainder of the proteins affected by 1,25-(OH)2D3 were unique to the subclone. With the exception of protein 304, the changes induced by 1,25-(OH)2D3 differed from those induced by triamcinolone acetonide, suggesting that unique proteins modulate the osteoblastic phenotype in response to these steroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2328702&dopt=Abstract triamcinolone Kenalog



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Delayed healing of muscle after injection of bupivicaine and steroid.

Guttu RL, Page DG, Laskin DM.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Medical College of Virginia, Richmond 23298.

The purpose of this study was to evaluate the histologic changes that occur in an area of rat skeletal muscle injected with a local anesthetic and steroid combination. Thirty adult male laboratory rats were assigned to one of six groups. Group 1 received bupivicaine injected into the right gastrocnemius muscle; Group 2 received procaine; Group 3 received bupivicaine and triamcinolone; Group 4 received procaine and triamcinolone; Group 5 received triamcinolone; and Group 6 received normal saline. Animals were sacrificed at 24 hours and at 1, 2, 3, and 4 weeks. The saline, steroid, and procaine groups showed minimal tissue reaction. The procaine/steroid group had focal areas of inflammation at 24 hours but none on subsequent evaluations. The bupivicaine group showed moderate localized necrosis of muscle fibers and a mild inflammatory cell response at 24 hours. Regeneration of muscle fibers was seen at 1 week, and at 3 weeks the tissue had returned to normal. The bupivicaine/steroid group showed extensive localized necrosis of muscle fibers with a heavy inflammatory cell response at 24 hours. These areas of necrosis persisted throughout the 4-week post-injection period, although some muscle fiber regeneration and fibrosis were also noted. This study shows that bupivicaine produces more tissue reaction than procaine and that the addition of steroid to bupivicaine increases the initial tissue damage and prolongs the healing phase.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2346299&dopt=Abstract triamcinolone Kenalog



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Radiographic followup of joints injected with triamcinolone hexacetonide for the management of childhood arthritis.

Sparling M, Malleson P, Wood B, Petty R.

Department of Medicine, University of British Columbia, Vancouver, Canada.

Evidence of deleterious effects following intraarticular injection of triamcinolone hexacetonide was sought through a review of radiographs of 145 joints of 55 children with chronic arthritis. Possible deleterious effects were noted in 16 joints of 11 patients. These effects included: small patella (2 joints), patellar osteochondritis dissecans (1 joint), periarticular calcification (9 joints), intraarticular tibial bony spur (1 joint), avascular necrosis of the distal radial epiphysis (2 joints), and avascular necrosis of the proximal femoral epiphysis (1 joint). Only the latter possible complication was symptomatic. Serial radiographs of 76 joints of 30 children showed mild progressive changes compatible with the underlying disease, except in the hip joint, where changes were more severe. The intraarticular injection of triamcinolone hexacetonide is a procedure that appears to be associated with an acceptably low frequency of radiologic abnormalities for many joints in children with chronic arthritis, but its effects on the hip joint remain uncertain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2363737&dopt=Abstract triamcinolone Kenalog