Kenalog
A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer.

Krishnan AV, Zhao XY, Swami S, Brive L, Peehl DM, Ely KR, Feldman D.

Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

The cortisol/cortisone-responsive AR (AR(ccr)) has two mutations (L701H and T877A) that were found in the MDA PCa human prostate cancer cell lines established from a castrated patient whose metastatic tumor exhibited androgen-independent growth. Cortisol and cortisone bind to the AR(ccr) with high affinity. In the present study, we characterized the structural determinants for ligand binding to the AR(ccr). Our data revealed that many of the C17, C19, and C21 circulating steroids, at concentrations that are found in vivo, functioned as effective activators of the AR(ccr) but had little or no activity via the wild-type AR or GRalpha. Among the synthetic glucocorticoids tested, dexamethasone activated both GRalpha and AR(ccr), whereas triamcinolone was selective for GRalpha. In MDA PCa 2b cells, growth and prostate-specific antigen production were stimulated by potent AR(ccr) agonists such as cortisol or 9alpha-fluorocortisol but not by triamcinolone (which did not bind to or activate the AR(ccr)). Of the potential antagonists tested, bicalutamide (casodex) and GR antagonist RU38486 showed inhibitory activity. We postulate that corticosteroids provide a growth advantage to prostate cancer cells harboring the promiscuous AR(ccr) in androgen-ablated patients and contribute to their transition to androgen-independence. We predict that triamcinolone, a commonly prescribed glucocorticoid, would be a successful therapeutic agent for men with this form of cancer, perhaps in conjunction with the antagonist casodex. We hypothesize that triamcinolone administration would inhibit the hypothalamic-pituitary-adrenal axis, thus suppressing endogenous corticosteroids, which stimulate tumor growth. Triamcinolone, by itself, would not activate the AR(ccr) or promote tumor growth but would provide glucocorticoid activity essential for survival.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11956172&dopt=Abstract triamcinolone Kenalog



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Comparison of skin stripping, in vitro release, and skin blanching response methods to measure dose response and similarity of triamcinolone acetonide cream strengths from two manufactured sources.

Pershing LK, Bakhtian S, Poncelet CE, Corlett JL, Shah VP.

Department of Dermatology, University of Utah School of Medicine, 4B454 SOM, 30 N. 1900 E., Salt Lake City, UT 84132, USA. pershing derm.med.utah.edu

The collective studies compare in vitro drug release, in vivo skin stripping, and skin blanching response methods for dose responsiveness and bioequivalence assessment of triamcinolone acetonide cream products, as a function of application duration, drug concentration, and manufacturer source. Commercially available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two manufacturers were evaluated in vitro for rate and extent of drug release across synthetic membranes and in vivo for rate, extent, and variability of drug uptake into human stratum corneum and skin blanching response in human forearm skin. Data demonstrate that increasing triamcinolone acetonide cream concentration applied increased the rate and extent of drug released in vitro as well as the extent of drug uptake and skin blanching response in human skin in vivo. No difference (p < 0.05) between the two sources of 0.1% or 0.5% creams was measured by the skin stripping or skin blanching response methods. Dermatopharmacokinetic analysis of triamcinonide acetonide in vivo is therefore dose responsive to drug concentration applied and application duration and agrees with in vivo skin blanching results. Data support the use of dermatopharmacokinetic methods for bioequivalence and bioavailability assessment of topical drug products. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11977107&dopt=Abstract triamcinolone Kenalog



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Simultaneous determination of terbinafine HCL and triamcinolone acetonide by UV derivative spectrophotometry and spectrodensitometry.

El-Saharty YS, Hassan NY, Metwally FH.

Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, El-Kasr, El-Aini St., ET-11562, Cairo, Egypt. ysaharty hotmail.com

A binary mixture of terbinafine hydrochloride and triamcinolone acetonide was determined by three different methods. The first one concerned with determination of both drugs using first derivative (D(1)) spectrophotometric technique at 297 and 274 nm over concentration ranges of 5-30 and 4-24 microg ml(-1), with mean percentage accuracies 99.90+/-0.67 and 100.25+/-0.49, respectively. The second method depends on ratio-spectra 1st derivative (RSD(1)) spectrophotometry at 298 and 248 nm over the same concentration ranges with mean percentage accuracies 100.22+/-0.51 and 99.93+/-0.56, respectively. The spectrodensitometric analysis provides a rapid and precise method for the separation and quantitation of both terbinafine hydrochloride and triamcinolone acetonide. The method depends on the quantitative densitometric evaluation of thin layer chromatogram of terbinafine hydrochloride and triamcinolone acetonide at 283 and 238 nm over concentration ranges of 5-25 and 2.5-22.5 microg spot(-1), with mean percentage accuracies 100.66+/-0.51 and 100.27+/-0.73, respectively. The suggested procedures were checked using laboratory prepared mixtures and were successfully applied for the analysis of their pharmaceutical preparations. The three methods retained their accuracy and precision when applying the standard addition technique. The results obtained by applying the proposed methods were statistically analysed and compared with those obtained by a reported method.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12008136&dopt=Abstract triamcinolone Kenalog



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Determination of methylparaben, propylparaben, triamcinolone acetonide and its degradation product in a topical cream by RP-HPLC.

Matysova L, Hajkova R, Sicha J, Solich P.

Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.

A novel reversed-phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of active component triamcinolone acetonide, its degradation product triamcinolone (occurring in formulation after long-term stability tests) and two preservatives presented in the cream-methylparaben and propylparaben, using hydrocortisone as an internal standard.The chromatographic separation was performed on a Supelco Discovery C18 column; the mobile phase for separation of all compounds consists of a mixture of acetonitrile and water (40:60 v/v). The analysis time was less than 9 min, at a flow rate of 0.6 mL min(-1) and detection at 240 nm. The method was found to be applicable for routine analysis (stability tests, homogeneity) in the pharmaceutical product topical cream Triamcinolon cream 0.1%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12819846&dopt=Abstract triamcinolone Kenalog



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Triamcinolone-assisted pars plana vitrectomy improves the surgical procedures and decreases the postoperative blood-ocular barrier breakdown.

Sakamoto T, Miyazaki M, Hisatomi T, Nakamura T, Ueno A, Itaya K, Ishibashi T.

Department of Ophthalmology, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-82, Japan. tsakamot eye.med.kyushu-u.ac.jp

PURPOSE: To determine the effect of a triamcinolone-assisted pars plana vitrectomy (PPV) on the visibility of hyaloid during surgery and the postoperative clinical outcome. METHODS: Thirty-one patients with proliferative retinal disease [8 with diabetic macular edema (DME), 10 with proliferative diabetic retinopathy (PDR), 13 with proliferative vitreoretinopathy (PVR)] underwent PPV, where the vitreous body was visualized by the intravitreal injection of triamcinolone solution during the operation. The visual acuity, intraocular pressure (IOP), tamponade, corneal pathology, after-cataract, vitreous hemorrhage, and necessity of reoperation, were thereafter examined for at least 3 months after surgery. The anterior chamber laser flare cell meter was used on postoperative day 8 in DME eyes with triamcinolone-assisted PPV and with routine PPV to evaluate the breakdown of the blood-ocular barrier. RESULTS: The vitreous body was clearly seen by means of triamcinolone during surgery, which greatly helped us to perform a posterior hyaloid resection safely and thoroughly. Six of 8 DME eyes, 8 of 10 PDR eyes, and 5 of 13 PVR eyes showed an improvement in their vision postoperatively. No eye except one experienced IOP elevation above 21 mmHg for 7 days. Six eyes had vitreous hemorrhage. The DME eyes which received triamcinolone-assisted PPV showed significantly less breakdown of the blood-ocular barrier than those with routine PPV (Mann-Whitney U-test, P<0.01). CONCLUSION: Triamcinolone improved the visibility of the hyaloid and the safety of the surgical procedures during PPV and also inhibited the postoperative breakdown of the blood-ocular barrier. Although the long-term effects are still unknown, this method appears potentially useful as an improved treatment for proliferative retinal diseases.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12107507&dopt=Abstract triamcinolone Kenalog



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Triamcinolone stimulates bFGF production and inhibits TGF-beta1 production by human dermal fibroblasts.

Carroll LA, Hanasono MM, Mikulec AA, Kita M, Koch RJ.

Wound Healing and Tissue Engineering Laboratory, Division of Otolaryngology/Head and Neck Surgery, Stanford University Medical Center, Stanford, California, USA. lcaroll uchospitals.edu

BACKGROUND: Triamcinolone acetonide has been shown to decrease both cellular proliferation and collagen production by dermal fibroblasts. An alteration of cytokine levels may mediate these effects. OBJECTIVE: To delineate the effect of triamcinolone acetonide on both cellular proliferation and the production of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) by human fibroblasts grown in a serum-free in vitro model. METHODS: Human normal and keloid dermal fibroblasts were propagated in a serum-free in vitro model with exposure to 0, 5, 10, or 20 microm triamcinolone acetonide for 0, 24, 72, or 96 hours. Cell counts were determined by phase contrast microscopy. Levels of bFGF and TGF-beta1 in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In our study, 20 microm triamcinolone acetonide caused statistically significant increases in the peak levels of bFGF for normal and keloid fibroblast cell lines (P < 0.05). It also caused statistically significant decreases in the level of TGF-beta1 for normal and keloid fibroblast cell lines. For the keloid fibroblasts, 10 microm triamcinolone acetonide also caused a statistically significant decrease in the level of TGF-beta1. CONCLUSION: We conclude from these results that triamcinolone acetonide increases the production of bFGF and decreases production of TGF-beta1 by human dermal fibroblasts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12174062&dopt=Abstract triamcinolone Kenalog