Synalar
[The synergistic effect of low-dose cyclosporine and fluocinolone acetonide on the survival of rat allogenic skin graft]

[Article in Chinese]

Zhao XF.

Either cyclosporine (CsA) or fluocinolone acetonide (FA) may prolong the survival of skin allografts. This study was performed to evaluate the effect of combination of these two treatments. BUF rat skin was transplanted to LEW rat. The mean survival time (MST) of control grafts was 9.9 days. In rats fed low dose CsA (2.5 or 5mg/kg/day, blood CsA 221 or 631 micrograms/ml), the MST were 16.0 days. When FA with or without CsA topically applied only, their MST were 22.7 or 24.1 days. If topical application of CsA + FA in combination with low dose oral CsA, the grafts survived indefinitely when the treatment was continued (100 days). The synergistic effect of CsA and topical FA is significant and provides a potential safe means for prolonging skin allograft survival following burn injury.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2620608&dopt=Abstract fluocinolone Synalar



Synalar
Effects of immunosuppressive chemicals on lymphoid development in foetal thymus organ cultures.

d'Argy R, Bergman J, Dencker L.

Department of Toxicology, Uppsala University, Sweden.

A murine foetal thymus organ culture system was employed to screen a number of immunotoxic chemicals for direct thymus toxicity. The toxic effects caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners on the system used had previously been shown to be similar to those caused in vivo on lymphoid development. The most potent compound tested was the corticosteroid fluocinolone acetonide, which caused a 50% inhibition of lymphoid development (EC50) at a concentration of 5 x 10(-11) M. The EC50 of TCDD was around 5 x 10(-10) M while that of 4 beta-phorbol 12-myristate 13-acetate (TPA) was ca 10(-7) M. TCDD and its congeners are believed to act via binding to the Ah receptor. Other known or presumed ligands of this receptor, which are potent inducers of P1-450 (P-448) -dependent polysubstrate monooxygenase activities, were considerably less toxic with EC50 levels varying between 10(-5) M (7,12-dimethylbenz(alpha-) antracene, alpha-naphthoflavone, benzo(alpha)pyrene) and 10(-4) M (beta-naphthoflavone and 3-methylcholantrene). Dinaphtho/2,3-b,5,6-b/dioxin and indolo/2,3-b/carbazole showed toxicity at 5 x 10(-6)-10(-5) M and 5 x 10(-5) M respectively. TCDD, TPA, and fluocinolone showed additive effects when added two by two in different combinations. Thus fluocinolone, known to counteract the toxicity and epidermal growth factor (EGF) cell-surface receptor-decreasing activity caused by TPA in other cell types, failed to decrease TPA toxicity in the thymus culture system.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2755908&dopt=Abstract fluocinolone Synalar



Synalar
Further evidence for the involvement of gap-junctional intercellular communication in induction and maintenance of transformed foci in BALB/c 3T3 cells.

Yamasaki H, Katoh F.

International Agency for Research on Cancer, Lyon, France.

In order to investigate further the role of gap-junctional intercellular communication in the process of cell transformation, we examined the effects of chemicals that modulate gap-junctional communication on the induction and maintenance of transformed foci in BALB/c 3T3 cells. When dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone was added during the induction of cell transformation by standard (3-methylcholanthrene alone) or two-stage (low dose of 3-methylcholanthrene plus phorbol ester) protocols, there was a significant decrease in the number of transformed foci. When BALB/c 3T3 cells are transformed, there is selective intercellular communication between transformed and between surrounding nontransformed cells: transformed cells communicate among themselves but not with surrounding normal cells. Addition of dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone to culture dishes in which transformed foci were present induced communication between transformed cells and surrounding normal cells. In the continuous presence of these chemicals, there was a clear decrease in the number of transformed foci. These chemicals therefore appear capable of reestablishing intercellular communication between transformed and nontransformed cells and of diminishing the number of transformed foci. However, when transformed cells were isolated and placed in culture dishes at clonal density in the presence of these chemicals, there was hardly any decrease in the number of transformed colonies, suggesting that the chemicals cannot revert the phenotype of transformed cells in the absence of normal cells. These results suggest that chemicals that modulate intercellular communication not only inhibit the induction of transformed foci but also revert transformed cells to the normal phenotypes by establishing intercellular communication with surrounding normal cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2836057&dopt=Abstract fluocinolone Synalar



Synalar
Enhancement of beta-propiolactone tumorigenesis in mouse skin by pretreatment with the anti-inflammatory steroid fluocinolone acetonide.

Woodworth BA, Scribner JD, Scribner NK.

Using a two-step carcinogenesis protocol, SENCAR mice were initiated with 25 micrograms 7,12-dimethylbenz[a] anthracene (DMBA) and were then treated twice weekly with either (a) 0.5 mg beta-propiolactone (BPL) or (b) 1 microgram fluocinolone acetonide (FA) followed in 30 min by 0.5 mg BPL. The tumor incidence for the group receiving FA prior to BPL was significantly greater than for BPL alone (P less than 0.0005). Under these experimental conditions, BPL alone showed neither promoting activity nor complete carcinogenic activity. These results were not anticipated, but the reasons for their occurrence are being explored.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3087615&dopt=Abstract fluocinolone Synalar



Synalar
Relative lack of systemic effects of mometasone furoate on Langerhans cells of mice after topical administration as compared with other glucocorticosteroids.

Belsito DV, Baer RL, Schultz JM, Thorbecke GJ.

Department of Dermatology, New York University School of Medicine, New York.

The effects of topically applied mometasone furoate were compared with those of other glucocorticosteroids, in particular fluocinolone acetonide, in assays of murine epidermal Ia+ Langerhans cell density. No evidence of systemic effects, as determined by a decline in the density of Ia+ LC in distant sites, was detected after local topical applications (5 times a week) of mometasone furoate 0.001% for periods of up to 3 weeks. Other steroids, even in such very low concentrations, and mometasone furoate in higher concentrations, produced systemic effects on Ia+ LC when used for longer than 5 d. The recovery time of Ia+ Langerhans cells is significantly shorter after application of mometasone furoate than after fluocinolone acetonide. However, with both compounds, recovery occurred more rapidly after 3 weeks than after a 1- or 2-week interval of compound administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3166025&dopt=Abstract fluocinolone Synalar