Synalar
The effect of combined immunosuppression with systemic low-dose cyclosporin and topical fluocinolone acetonide on the survival of rat hind-limb allografts.

Inceoglu S, Siemionow M, Chick L, Craven CM, Lister GD.

Gazi University Hastanesi Besevler, Ankara, Turkey.

Sixty rat hind-limb allotransplantations across strong histocompatibility barriers were performed. Group I (isograft controls), (Lewis-Brown-Norway [LBN] to LBN) limb transplantations were performed; Group II (rejection controls), LBN limbs transplanted to Lewis rat LEW recipients with no immunosuppressive treatment; Group III (steroid group), fluocinolone acetonide (50 micrograms/ml) was applied topically; Group IV (cyclosporine group), 4 mg/kg of cyclosporine was administered subcutaneously daily; Group V (combination group), combined systemic cyclosporine with topical fluocinolone acetonide was administered daily. Group II: Limb rejection was present on the fourth day. Group III: Limb survival was extended for 3 weeks with no signs of skin rejection in 75% of animals. Group IV: Rejection was complete at 3 weeks. Group V: Limbs survived to 6 weeks. Topical steroid prevented skin rejection and delayed rejection of other components of the composite allograft. Combined treatment of topical steroid and low cyclosporine doses significantly extended survival rate of limb allografts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7944198&dopt=Abstract fluocinolone Synalar



Synalar
Topical formulations of fluocinolone acetonide. Are creams, gels and ointments bioequivalent and does dilution affect activity?

Gao HY, Li Wan Po A.

Drug Delivery Research Group, School of Pharmacy, Queen's University of Belfast, UK.

The study was done in healthy volunteers to investigate the vasoconstrictor activity of three commercially available formulations of fluocinolone acetonide (Synalar gel, cream and ointment) and to determine whether they were bioequivalent. The influence of dilution of the cream formulation on activity was also examined. Twenty mg of each topical formulation was applied, followed by occlusion for 6 h, and the potency was evaluated by measuring the vasoconstrictor effect using tristimulus colour analysis. The cream formulation was more potent than the ointment, with the gel having intermediate strength. Dilution did not significantly reduce activity. While choice of an appropriate topical corticosteroid formulation largely depends on the nature of the lesions, this study has shown that different formulations of nominally the same concentration have different potencies; dilution up to 1 in 10 produced no significant reduction in potency. The potency classification in the British National Formulary for formulations of Synalar may need revision.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8005190&dopt=Abstract fluocinolone Synalar



Synalar
Blocking of tumor promoter-induced AP-1 activity inhibits induced transformation in JB6 mouse epidermal cells.

Dong Z, Birrer MJ, Watts RG, Matrisian LM, Colburn NH.

Biological Carcinogenesis and Development Program, PRI/DynCorp, Frederick, MD.

AP-1 transcriptional activity is stimulated by the transformation promoters phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate," TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. Although TPA stimulates expression of the jun and fos family genes, only c-jun expression shows higher elevation in P+ cells than in P- cells. The present study tests the hypothesis that induced AP-1 activity is required for tumor promoter-induced transformation in JB6 P+ cells. Both retinoic acid and the glucocorticoid fluocinolone acetonide inhibited basal and TPA-induced AP-1 activities that were tested with a stromelysin promoter-chloramphenicol acetyltransferase reporter gene in P+ cells. Since both retinoic acid and fluocinolone acetonide are active in inhibiting TPA-induced anchorage-independent transformation of P+ cells in the dose range that blocks TPA-induced AP-1 activity, their antipromoting effects may occur through inhibition of AP-1 activity. To test the hypothesis with a more specific inhibitor, stable clonal transfectants of P+ cells expressing dominant negative c-jun mutant encoding a transcriptionally inactive product were analyzed. All transfectants showed a block in TPA and EGF induction of AP-1 activity. All transfectants also showed inhibition of TPA-induced transformation, and most transfectants showed a block in EGF-induced transformation. These results indicate that AP-1 activity is required for TPA- or EGF-induced transformation. This work demonstrates that a specific block in induced AP-1 activity inhibits tumor promoter-induced transformation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8290571&dopt=Abstract fluocinolone Synalar



Synalar
Chemical stability of fluocinolone acetonide ointment and fluocinonide cream diluted in emollient bases.

Barnes AR, Chapman SB, Irwin WJ.

Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham, UK.

The chemical stability of fluocinolone acetonide ointment and fluocinonide cream was studied when diluted in emollient bases. Fluocinolone acetonide ointment was diluted 1 in 4 with Unguentum Merck and Lipobase. Fluocinonide cream was also studied in these bases, with the addition of Metosyn Diluent, at dilutions of 1 in 4 and 1 in 10. Regression analysis gave the time for 5% degradation of fluocinolone acetonide at a dilution of 1 in 4 in Unguentum Merck and in Lipobase as 12 weeks in both cases. The lower 95% confidence bound of each regression line was used to set shelf lives, for additional safety, and gave values of 1 month for the Unguentum Merck dilution and 2 months for the Lipobase dilution. Fluocinonide dilutions were more stable than the corresponding fluocinolone acetonide dilutions, with no degradation detectable during the study. The base made no observable difference to stability. Shelf lives, based on the lower 95% confidence bound of the regression data, of more than 6 months would be feasible for all of the fluocinonide 1 in 4 dilutions studied and for the 1 in 10 dilution in Unguentum Merck. However, for fluocinonide 1 in 10 in Metosyn Diluent, a shelf life of only 6 weeks could be assured, due to there being more variation in the analytical results. There were insufficient data to determine a storage life based on the lower 95% confidence bound of the regression for fluocinonide 1 in 10 in Lipobase. More data would be required to determine if there was significant interbatch variation in the stability of the dilutions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8576293&dopt=Abstract fluocinolone Synalar



Synalar
Mechanism of skin tumorigenesis by contact sensitizers: the effect of the corticosteroid fluocinolone acetonide on inflammation and tumor induction by 2,4 dinitro-1-fluorobenzene in the skin of the TG.AC (v-Ha-ras) mouse.

Albert RE, French JE, Maronpot R, Spalding J, Tennant R.

University of Cincinnati Medical Center, Department of Environmental Health, OH 45267-0056, USA.

The effect of the corticosteroid fluocinolone acetonide (FA) on skin tumor induction and inflammation by the contact sensitizer dinitrofluorobenzene (DNFB) was examined. This study broadly relates to the question of whether contact sensitizers, as electrophilic chemicals that produce protein adduction, may constitute an environmental cancer hazard. The specific aim of this study was to evaluate the extent to which the immunogenic inflammatory response to DNFB, in contrast to DNFB cytotoxicity, might be responsible for tumor induction. Experiments were conducted on a transgenic (TG.AC) mouse, incorporating a mutated ras oncogene (v-Ha-ras) that responds rapidly and profusely with skin papillomas to tumor promoters as if it were genetically initiated. Various doses and patterns of DNFB and FA were applied to the skin in a 2-week period; DNFB was given four times and FA was given either with the DNFB or daily. The tumor response to DNFB was completed by 8 weeks from the first dose and was consistent with a dose-squared relationship. FA was not tumorigenic alone; when given with DNFB, it caused only a small reduction in inflammation and tumor yield. When given daily, FA increased ulcerative skin damage, inflammation, and the yield tumors. The results suggest that tumorigenesis by DNFB, in the high-dose short-term regimen used here, is mainly due to its cytotoxicity and not contact sensitization.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8930547&dopt=Abstract fluocinolone Synalar