1.Selective Activator of the Glucocorticoid Receptor Compound A Dissociates Therapeutic and Atrophogenic Effects of Glucocorticoid Receptor Signaling in Skin.
Anna KLOPOT ; Gleb BAIDA ; Pankaj BHALLA ; Guy HAEGEMAN ; Irina BUDUNOVA
Journal of Cancer Prevention 2015;20(4):250-259
BACKGROUND: Glucocorticoids are effective anti-inflammatory drugs widely used in dermatology and for the treatment of blood cancer patients. Unfortunately, chronic treatment with glucocorticoids results in serious metabolic and atrophogenic adverse effects including skin atrophy. Glucocorticoids act via the glucocorticoid receptor (GR), a transcription factor that causes either gene transactivation (TA) or transrepression (TR). Compound A (CpdA), a novel non-steroidal GR ligand, does not promote GR dimerization and TA, retains anti-inflammatory potential but induces fewer metabolic side effects compared to classical glucocorticoids when used systemically. As topical effects of CpdA have not been well studied, this work goal was to compare the anti-inflammatory and side effects of topical CpdA and glucocorticoids and to assess their effect on GR TA and TR in keratinocytes. METHODS: We used murine immortalized keratinocytes and F1 C57BlxDBA mice. Effect of glucocorticoid fluocinolone acetonide (FA) and CpdA on gene expression in keratinocytes in vitro and in vivo was evaluated by reverse transcription-PCR. The anti-inflammatory effects were assessed in the model of tumor promoter 12-O-tertradecanoyl-acetate (TPA)-induced dermatitis and in croton oil-induced ear edema test. Skin atrophy was assessed by analysis of epidermal thickness, keratinocyte proliferation, subcutaneous adipose hypoplasia, and dermal changes after chronic treatment with FA and CpdA. RESULTS: In mouse keratinocytes in vitro and in vivo, CpdA did not activate GR-dependent genes but mimicked closely the inhibitory effect of glucocorticoid FA on the expression of inflammatory cytokines and matrix metalloproteinases. When applied topically, CpdA inhibited TPA-induced skin inflammation and hyperplasia. Unlike glucocorticoids, CpdA itself did not induce skin atrophy which correlated with lack of induction of atrophogene regulated in development and DNA damage response 1 (REDD1) causatively involved in skin and muscle steroid-induced atrophy. CONCLUSIONS: Overall, our results suggest that CpdA and its derivatives represent novel promising class of anti-inflammatory compounds with reduced topical side effects.
Animals
;
Atrophy
;
Croton
;
Cytokines
;
Dermatitis
;
Dermatology
;
Dimerization
;
DNA Damage
;
Ear
;
Edema
;
Fluocinolone Acetonide
;
Gene Expression
;
Glucocorticoids
;
Humans
;
Hyperplasia
;
Inflammation
;
Keratinocytes
;
Matrix Metalloproteinases
;
Mice
;
Receptors, Glucocorticoid*
;
Skin*
;
Transcription Factors
;
Transcriptional Activation
2.A Case of Refractory Behcet's Uveitis Improving after Insertion of Fluocinolone Acetonide Implant.
Yun Sung KIM ; Jung Ran CHOI ; Seok Won KIM ; Hyun Sook KIM
Journal of Rheumatic Diseases 2013;20(2):123-126
Behcet's disease (BD) is systemic vasculitis that can manifest severely debilitating. Despite the understanding mechanisms of overall BD, there are remains many questions in various critical manifestations and treatments. The ocular manifestation is characterized by a prototype of chronic relapsing and persistent uveitis. The main treatment is topical corticosteroid, and topical nonsteroidal anti-inflammatory drugs in mild uveitis. The recurrent and severe uveitis could be treated with ocular corticosteroid injections, and systemic corticosteroid for inducing long-lasting suppression of the inflammation. Systemic corticosteroids should rapidly be tapered within weeks for avoiding side effects. Recent advances have led to the development of sustained-release corticosteroid devices using different corticosteroids. We present a case of 67-year-old woman who received a fluocinolone acetonide implant for recurrent Behcet's uveitis. She was successfully treated with implant and the uveitis became quiescent within a month.
Adrenal Cortex Hormones
;
Female
;
Fluocinolone Acetonide
;
Humans
;
Inflammation
;
Systemic Vasculitis
;
Uveitis
3.A Case of Retiserttrade mark Implant for Chronic Behcet's Panuveitis.
Journal of the Korean Ophthalmological Society 2008;49(6):1007-1012
PURPOSE: Retisert(TM) (fluocinolone acetonide implant) has recently been approved for clinical use in patients with noninfectious posterior uveitis. We report a patient with intractable chronic Behcet's panuveitis who underwent Retisert(TM) implantation and showed a favorable outcome. METHODS: A 30-year-old male affected with intractable Behcet's uveitis of both eyes for over one year which did not respond to oral steroids and immunosuppressants; subcutaneous interferon injection caused undesirable side effects such as impotency and pyrexia. Initial visual acuities were 20/1000 in the right eye and 20/100 in the left eye, and both eyes showed severe panuveitis with posterior subcapsular cataract, especially in the right eye. The subtenon triamcinolone injection was performed in the right eye, which was only effective to anterior uveitis, and Retisert(TM) was implanted in the right eye after the cataract operation. Two months later the visual acuity increased to 20/25, and the inflammation was totally controlled. There were no ocular or systemic adverse events. CONCLUSIONS: Retiserttrade mark is a fast, effective, and safe treatment for chronic, non.infectious posterior uveitis.
Adult
;
Cataract
;
Eye
;
Fever
;
Fluocinolone Acetonide
;
Humans
;
Inflammation
;
Interferons
;
Male
;
Panuveitis
;
Steroids
;
Triamcinolone
;
Uveitis
;
Uveitis, Anterior
;
Uveitis, Posterior
;
Visual Acuity
4.Fluoride in the water resources in the Tam Diep, Vinh Quynh, Dinh Cong and Van Phuc, Thanh Tri Hanoi
Journal of Vietnamese Medicine 2002;269(2):36-39
Some indicators of the water from rain, well, river, pond, lake drilling well, especially fluoride in the contaminated water resources in Vinh Quynh and Tam Diep communes and Van Phuc, Dinh Cong communes (control), Thanh Tri district, Hanoi were analysed. The concentration of fluoride, PH, and water’s hardness- and the rate of the enamel disorder in children with ages of 6-12 in Tam Diep and Van Phuc commune were determined. The results have shown that the concentration of fluoride in all water resources was low and threr is a significant difference from the contaminated areas and control.
Fluocinolone Acetonide
;
Pharmacokinetics
;
Pharmaceutical Preparations
5.Studying influences of some factors on ability of release and trandermal absorption of fluocinolone acetonid
Pharmaceutical Journal 2000;291(7):14-17
The influence of different ointment bases and percutaneous penetration enhancers on in vitro release and anti-inflammatory efficacy of Fluoci-nolone acetonide was studied. The rank order of release through dialysis membrane was as follow: PEG> gel CMC> gel HPMC> gel carbopol> emugel>emultion. The anti-inflammatory efficacy of Fluocinolone acetonide on hairless rat skin was as follow: gel HPMC+0.5% I-menthol>gel carbopol +0.5% I-menthol > gel carbopol +0.5% I-methol > gel carbopol > oleaginous bases.
Fluocinolone Acetonide
;
Pharmacokinetics
;
Pharmaceutical Preparations
6.Assessment of Atrophy of Human Epidermis Caused by Various Corticosteroids Using Chamber Occlusion and Histometry.
Young Il CHUN ; Joon Mo YANG ; Myoung Soo SUH ; Hee Chul EUN ; Yoo Shin LEE
Korean Journal of Dermatology 1986;24(5):579-585
The aim of this stud y was to compare the epidermal thinning properties of four corticosteroid ointments applied under occlusion, using histology and histometry. The results were surnmerized as follows: 1.The stratum corneurn was dramatically thinned, appearing as a wispy layer of horny cells as apposed to the norrnal basket-weave configuration. this effect was prominent at sites treated with clobestasol propionate, fluocinonide, and fluocinolone acetonide. 2. With the histometry, visible epidermal thickness wa.s markedly reduced. This effect w is prominent in the following ascending order: fluocinolone acetonide, fluocienonide, clobestasol-17-propionate. Hydrocortisone was the least atrophogenic. 3. Clohestasol-17-propionate and fluocinonide caused significant flattening of dermo-epidermal junction, Fluocinolone acetonide and hydrocortisone caused less pronounced cbanges. 4. Marked capillary dilation af papilly dermis is caused by clobestasol-17-propionate, fluocinonide and fluocinolone acetonide.
Adrenal Cortex Hormones*
;
Atrophy*
;
Capillaries
;
Dermis
;
Diethylpropion
;
Epidermis*
;
Fluocinolone Acetonide
;
Fluocinonide
;
Humans*
;
Hydrocortisone
;
Ointments
7.A Case of Pretibial Myxedema.
Eun Jung CHUNG ; Dae Gyu BYUN ; Hyung Ok KIM ; Chung Won KIM ; Won HOUH
Korean Journal of Dermatology 1981;19(6):969-973
Pretibial myxedema is a condition in which there is loeal thickening of the skin by a mucin-like deposit; it is nearly always asosciated with ophthalmopathy and thyrotoxicosis, not infrequently becomes more pronounced after treatrnent of thyrotoxicosis. The precise cause of pretibial myxedema is not known, but it appears that IgG LATS represents an autoantibody against a thyroid antigen, retroorbital tiesue and tbe skin, so, pretibial myxedema is presumed to be the result of a local antigen-antibody tissue reaction. A 57-year-old man had the history of diabetes since 1964 and Graves disease since May 1980, he was treated with metimazole for 1 month, with improving thyrotoxicosis but developed the pretibial myxedema. The histologic findings showed considerable amount of mucin, especially hyaluronic acid with toluidin blue stain at PH 3.0. The lesions were improved by local application of 0.01 x fluocinolone acetonide ointment with occlusive dressing technique.
Fluocinolone Acetonide
;
Graves Disease
;
Humans
;
Hyaluronic Acid
;
Hydrogen-Ion Concentration
;
Immunoglobulin G
;
Long-Acting Thyroid Stimulator
;
Middle Aged
;
Mucins
;
Myxedema*
;
Occlusive Dressings
;
Skin
;
Thyroid Gland
;
Thyrotoxicosis
8.A Study on the Effect of Topical Nonsteroidal Anti - inflammatory Drugs And Cortisosteroids on Ultraviolet Light - Induced Erythema.
Korean Journal of Dermatology 1980;18(2):115-120
lt is generally beIieved that several chemical mediators such as histamine, kinine, prustaglandin E and lysosomal enzyme are related to the pathogenesis of sunburn, but the exact mechenism of erythema is unknown. Recently, prostaglandins appear to be important mediators of ultraviolet erythema (UV-erythema) and several investigators has reported that the nonsteroidal antiinflammatory druga and corticosteroids supressed UV-erythema by inhibition of prostaglandin synthesis. This study was undertaken to evaluate the effect of topical nonsteroidaI antiinflammatary drugs and corticosteroids on UV-erythema induced by a artificial sunlamp. Nonsteroidal anti-inflammatory drugs (5% Bufexamac cream, 5% Ibuprofen cream, 5% Indomethacin cream) and corticosteroids(0.05% Fluocinonide cream, 0.5% Fluocortolone oint., 1%, Hydrocortisone cream) were applied immediately after 3~4 minimal erythema dose(MED) irradiation on back skin of 40 healthy volunteers and the delayed UV-erythema response was evaluated at 2, 4, 6, 8, 12, 24, 48 and 72 hours after irradiation, respectively. The resulta were as follows; 1) Minimal erythema dose(MED) was noted 4min. (62.5%), 3min. (25.0%), 5min. (22.5%). The averaged MED was 3. 63min. 2, MED has to be increased on site, applied nonsteroid and steroid agents topically, comparing with control site. 3) Blanching effect was detected in all cases of nonsteroid and steroid agents applicated topically, but in control site. 4) Average score in blanching effect was highest in 5% Indomethacin cream among nonsteroid agents(average score-2. 47) and 1% Hydrocortisone cream (average scoro -2. 63) among steroid agents.
Adrenal Cortex Hormones
;
Bufexamac
;
Erythema*
;
Fluocinonide
;
Fluocortolone
;
Healthy Volunteers
;
Histamine
;
Humans
;
Hydrocortisone
;
Ibuprofen
;
Indomethacin
;
Prostaglandins
;
Research Personnel
;
Skin
;
Sunburn
;
Ultraviolet Rays*
9.Therapeutic Experience with Clocortolone Pivalate.
Eun Jung CHYUNG ; Kang Woo LEE ; Chung Won KIM
Korean Journal of Dermatology 1977;15(4):443-446
Puraotix-C(0.1% Clocortolone Picalats Cream) is a new di-halogenated topical corticosteroid, and used in trial for treating several kinds of dermatoses. We treated 30 patients with Purantix-C who had one of the following dermatoses; atopic dermatitis, neurodermatitis, pustulosis palmaris et plantsris, seborrheic dermatitis, pityriasis rosea, nummular eczema, psoriasis vulgaris, pruritus ani and pompolyx. Among these 30 patients, Purantix-C showed excellent or good result (66.7%) either unoccluded or occluded application, 2~3 times daily for 7~10 days. Comparing with Lidex(0.05% fluorocinonide cream) and purantix-C, both of them had similar effect on eczema and psoriatic groups but Lidex was more effective than Purantix-C for treating the patients with the pustulosis palmaris et plantaris. Purantix-C without containing perfume and coloring substapce was less irritative.
Dermatitis, Atopic
;
Dermatitis, Seborrheic
;
Eczema
;
Fluocinonide
;
Humans
;
Neurodermatitis
;
Perfume
;
Pityriasis Rosea
;
Pruritus Ani
;
Psoriasis
;
Skin Diseases
10.Clinical experience with Fluocinonide cream.
Korean Journal of Dermatology 1975;13(2):109-112
Lidex(Fluacinonide) 0.05% in FAPG base is a new fluorinated topical corticosteroid. 30 patients with different steroid responsive dermatoaes were treated with 0. 05% Lidex. The diagnosis included atopic dermatitis, contact dermatitis, neurodermatitis, seborheic dermatitis, nummular eczema, psoriasis vulgaris, chronic eczema and pustulosis pahmaris et plantaris. In the majority of cases Lidex cream produced excellent to good result(70%) after unoccluded application 3 times daily for 10 days. Two patients complained burning or itching sensation after the initial application of Lidex. 0.05% Lidex was compared with 0. 25% Desoxymethasone cream and 0. 25% Fluocortolone cream and was found slightly more effective in Lidex.
Burns
;
Dermatitis
;
Dermatitis, Atopic
;
Dermatitis, Contact
;
Desoximetasone
;
Diagnosis
;
Eczema
;
Fluocinonide*
;
Fluocortolone
;
Humans
;
Neurodermatitis
;
Pruritus
;
Psoriasis
;
Sensation

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