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Pharmaceutics May 2020Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological...
Salvianolic Acid B in Microemulsion Formulation Provided Sufficient Hydration for Dry Skin and Ameliorated the Severity of Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.
Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determine the optimum vehicle for salvianolic acid B, investigate its therapeutic effect on psoriatic-like skin conditions, and explore its underlying mechanisms of action. BALB/c mice were administered topical imiquimod to induce psoriasis-like skin and were then randomly assigned to control, vehicle control, salvianolic acid B in vehicles, and 0.25% desoximetasone ointment treatment groups. Barrier function, cytokine expression, histology assessment, and disease severity were evaluated. The results showed that salvianolic acid B-containing microemulsion alleviated disease severity, reduced acanthosis, and inhibited interleukin-23/interleukin-17 (IL-23/IL-17) cytokines, epidermal proliferation, and increased skin hydration. Our study suggests that salvianolic acid B represents a possible new therapeutic drug for the treatment of psoriasis. In addition, such formulation could obtain high therapeutic efficacy in addition to providing sufficient hydration for dry skin.
PubMed: 32429542
DOI: 10.3390/pharmaceutics12050457 -
Archives of Dermatology Sep 1986This study was undertaken to determine whether the commonly used treatment of psoriasis with potent topical glucocorticoids results in hypercortisolism and whether...
This study was undertaken to determine whether the commonly used treatment of psoriasis with potent topical glucocorticoids results in hypercortisolism and whether metabolic changes might provide a means for monitoring pharmacologic effects of excessive systemic absorption of glucocorticoids. Plasma cortisol, glucose, and insulin and circulating polymorphonuclear leukocytes were assessed under controlled conditions in five otherwise healthy patients with psoriasis (40% to 85% involvement) treated with topical desoximetasone, without occlusion. In all patients, there were rapid and sustained suppression of endogenous cortisol production, twofold to threefold increases in fasting insulin levels indicating insulin resistance, and elevated levels of polymorphonuclear leukocytes. Two patients also experienced reduced glucose tolerance. These findings suggest that application of potent corticosteroids to large areas of diseased skin results in sufficient systemic absorption to cause not only adrenal suppression but some degree of hypercortisolism with greater frequency and rapidity than has been suggested. Prospective monitoring of insulin-glucose relationships as a sensitive index of the metabolic effects of glucocorticoids may provide a means of assessing excess systemic absorption that is not predictable on the basis of adrenal suppression or circulating levels of the drug. Such prediction could have particular relevance in anticipating adverse clinical effects in the treatment of chronic skin disorders with potent topical glucocorticoids.
Topics: Administration, Topical; Adult; Blood Glucose; Desoximetasone; Dexamethasone; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Insulin Resistance; Leukocyte Count; Male; Psoriasis; Skin Absorption
PubMed: 3527074
DOI: No ID Found -
Pharmaceutics Mar 2020Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery...
Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery system that may be used to deliver desoximetasone via topical product application in order to mitigate common side effects associated with traditional oral delivery routes. The aim of this research was to identify the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of drug-loaded niosomes using a systematic quality by design (QbD) approach. An organic phase injection method was developed and used to manufacture the niosomes. The CMAs were identified to be drug amount, concentrations of surfactant and cholesterol, and types of lipids. The CPPs were phase volumes, temperature, mixing parameters, and addition rate based on previous research. The quality attributes measured were entrapment efficiency, particle size distribution, PDI, and zeta potential. These were used to determine the quality target product profile (QTPP) of niosomes. The experimental data indicate that the critical impacting variables for niosomes are: surfactant and cholesterol concentrations, mixing parameters, and organic-phase addition rate. Based on the experimental results of this study methanol:diethyl ether (75:25) as the organic system, drug:surfactant:cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate is the ideal combination to achieve desirable desoximetasone niosomes with optimum entrapment efficiency and particle size for topical application.
PubMed: 32182792
DOI: 10.3390/pharmaceutics12030246 -
Contact Dermatitis Jul 1983A double blind, placebo-controlled treatment with Antabuse was carried out in 24 patients with hand eczema and nickel allergy. The amount of Antabuse given was gradually... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A double blind, placebo-controlled treatment with Antabuse was carried out in 24 patients with hand eczema and nickel allergy. The amount of Antabuse given was gradually increased from 50 to 200 mg daily. The maximum dose was given for 6 weeks. During the treatment period, the dermatitis of 5 out of 11 patients in the group treated with Antabuse healed, compared with 2 out of 13 in the group receiving the placebo. A statistical analysis was made of changes observed during the study, through the parameters: scaling, frequency of flares, erythema, area involved and number of vesicles. Differences in results obtained with Antabuse and the placebo were statistically significant only for the parameters scaling and frequency of flares (p less than 0.05). The difference between the sums of parameters following the 2 forms of treatment was not statistically significant (p = 0.11). 2 patients treated with Antabuse showed signs of hepatic toxicity; 1 of them had toxic hepatitis. No other significant side effects were seen.
Topics: Adult; Aged; Clinical Trials as Topic; Dermatitis, Atopic; Dermatitis, Contact; Desoximetasone; Disulfiram; Double-Blind Method; Drug Therapy, Combination; Female; Hand Dermatoses; Humans; Middle Aged; Nickel; Random Allocation
PubMed: 6352169
DOI: 10.1111/j.1600-0536.1983.tb04394.x -
Skin Research and Technology : Official... Feb 2009Operator-independent assessment of skin blanching is important in the development and evaluation of topically applied steroids. Spectroscopic instruments based on... (Comparative Study)
Comparative Study
BACKGROUND
Operator-independent assessment of skin blanching is important in the development and evaluation of topically applied steroids. Spectroscopic instruments based on hand-held probes, however, include elements of operator dependence such as difference in applied pressure and probe misalignment, while laser Doppler-based methods are better suited for demonstration of skin vasodilatation than for vasoconstriction.
OBJECTIVE
To demonstrate the potential of the emerging technology of Tissue Viability Imaging (TiVi) in the objective and operator-independent assessment of skin blanching.
METHODS
The WheelsBridge TiVi600 Tissue Viability Imager was used for quantification of human skin blanching with the Minolta chromameter CR 200 as an independent colorimeter reference method. Desoximetasone gel 0.05% was applied topically on the volar side of the forearm under occlusion for 6 h in four healthy adults. In a separate study, the induction of blanching in the occlusion phase was mapped using a transparent occlusion cover.
RESULTS
The relative uncertainty in the blanching estimate produced by the Tissue Viability Imager was about 5% and similar to that of the chromameter operated by a single user and taking the a(*) parameter as a measure of blanching. Estimation of skin blanching could also be performed in the presence of a transient paradoxical erythema, using the integrated TiVi software. The successive induction of skin blanching during the occlusion phase could readily be mapped by the Tissue Viability Imager.
CONCLUSION
TiVi seems to be suitable for operator-independent and remote mapping of human skin blanching, eliminating the main disadvantages of methods based on hand-held probes.
Topics: Colorimetry; Equipment Design; Equipment Failure Analysis; Erythrocyte Count; Humans; Image Interpretation, Computer-Assisted; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Skin; Skin Pigmentation; Tissue Survival
PubMed: 19152574
DOI: 10.1111/j.1600-0846.2008.00346.x -
Contact Dermatitis Dec 1996
Topics: Administration, Topical; Anti-Inflammatory Agents; Chronic Disease; Dermatitis, Allergic Contact; Desoximetasone; Drug Eruptions; Emulsions; Erythema Multiforme; Follow-Up Studies; Glucocorticoids; Humans; Leg; Male; Middle Aged; Ointments; Patch Tests; Recurrence; Venous Insufficiency; Zinc Oxide
PubMed: 9118633
DOI: 10.1111/j.1600-0536.1996.tb02419.x -
Contact Dermatitis Oct 1989
Topics: Administration, Cutaneous; Administration, Oral; Adult; Dermatitis, Contact; Desoximetasone; Dexamethasone; Drug Eruptions; Humans; Male; Patch Tests; Triamcinolone Acetonide
PubMed: 2532114
DOI: 10.1111/j.1600-0536.1989.tb03212.x -
Skin Pharmacology and Applied Skin... 2000The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in...
The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristics of this steroid, a new compound created according to an identical concept, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halogenated monoester desoximetasone 21-cinnamate (DCE) were tested and compared to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammatory processes in the epidermis, fibroblasts of the same origin were used to investigate the atrophogenic potential. Inflammation was induced by TNFalpha, resulting in an increased interleukin 1alpha (Il-1alpha) synthesis. As quantified by ELISA, all drugs significantly reduced Il-1alpha production. But PC and BMV appeared particularly potent, followed by DM and the two new congeners, which revealed minor anti-inflammatory activity. Glucocorticoid esters including PEP are rapidly degraded in keratinocytes (85% within 12 h). Hence, a ribonuclease protection assay of Il-1alpha mRNA was performed allowing short incubation times and thus minimizing biodegradation. This assay confirmed the anti-inflammatory potency of native PC and BMV. In contrary DCE and PEP did not reduce Il-1alpha mRNA to a significant extent. Therefore PEP acts as a prodrug only. In fibroblasts, Il-1alpha and Il-6 syntheses indicate proliferation and inflammation, respectively. Whereas PC and PEP inhibited Il-1alpha and Il-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly affected by the conventional glucocorticoids BMV and DM, but also by DCE. The minor unwanted effect of PC and PEP on fibroblasts was also reflected by their low influence on cell proliferation as derived from (3)H-thymidine incorporation. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticoids. In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of Il-1alpha) and antiproliferative effects in fibroblasts (suppression of Il-1alpha and Il-6; (3)H-thymidine incorporation) was analyzed. Here, PC is revealed as the only glucocorticoid with an improved benefit/risk ratio. Native PEP is shown to be almost ineffective and DCE presents exactly the opposite features of PC. It is tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts.
Topics: Administration, Topical; Anti-Inflammatory Agents; Cell Division; Cells, Cultured; Coloring Agents; Dermatitis; Desoximetasone; Enzyme-Linked Immunosorbent Assay; Glucocorticoids; Humans; Interleukins; Keratinocytes; NF-kappa B; Prednisolone; Protein Biosynthesis; RNA, Messenger; Ribonucleases; Risk Assessment; Signal Transduction; Skin; Tetrazolium Salts; Thiazoles; Thymidine
PubMed: 10754457
DOI: 10.1159/000029913 -
Biological & Pharmaceutical Bulletin Dec 2002The glucocorticoid receptor regulates gene expression mainly by two mechanisms; transactivation and trans-repression. A ligand with strong transrepression and weak... (Comparative Study)
Comparative Study
The glucocorticoid receptor regulates gene expression mainly by two mechanisms; transactivation and trans-repression. A ligand with strong transrepression and weak transactivation activity is predicted to be a beneficial agent with potent anti-inflammatory activity and minor adverse effects. Recently, the profile of a synthetic steroid, RU24858, has been reported to fulfill this condition in vitro, but others have reported no dissociation between the anti-inflammatory activity and side effects in vivo. To gain further information on the profile of this compound, we evaluated its transactivation ability using a reporter gene analysis both in vitro and in vivo. In the in vitro analysis, RU24858 demonstrated only a weak transactivation activity in HeLa cells, when compared with prednisolone. In CV-1 cells, however, these two glucocorticoids exhibited equivalent transactivation activities. This behavior is independent of whether the reporter gene is regulated by mouse mammary tumor virus promoter or multiple copies of glucocorticoid response element. When the reporter plasmid was inoculated into mouse abdominal skin using a gene gun, followed by orally administration of glucocorticoids, RU24858 induced significantly higher reporter enzyme activity than prednisolone. These results suggest that the profile of RU24858 is divergent and its transactivation ability is comparable to prednisolone depending on the cell-type both in vitro and in vivo.
Topics: Animals; Biolistics; Desoximetasone; Dose-Response Relationship, Drug; Glucocorticoids; HeLa Cells; Humans; Hydroxycorticosteroids; Ligands; Male; Mice; Mice, Inbred ICR; Plasmids; Rats; Receptors, Glucocorticoid; Transcriptional Activation; Tumor Cells, Cultured
PubMed: 12499651
DOI: 10.1248/bpb.25.1619 -
Pulmonary Pharmacology & Therapeutics 2008In inflammation, nitric oxide (NO) is produced by inducible nitric oxide synthase (iNOS) induced by bacterial products and cytokines, and NO acts as a regulatory and...
In inflammation, nitric oxide (NO) is produced by inducible nitric oxide synthase (iNOS) induced by bacterial products and cytokines, and NO acts as a regulatory and pro-inflammatory mediator. Glucocorticoids are powerful anti-inflammatory agents that inhibit the expression of iNOS and various other inflammatory factors. Histone deacetylation has been recently described as a novel mechanism how glucocorticoids down-regulate transcriptional activation of some inflammatory genes. The aim of the present study was to investigate the effects of inhibitors of histone deacetylation on the suppressive effects of glucocorticoids on NO production and iNOS expression. Dexamethasone and a dissociated glucocorticoid RU24858 inhibited NO production, and iNOS protein and mRNA expression in macrophages exposed to bacterial lipopolysaccharide (LPS). In the presence of a glucocorticoid receptor (GR) antagonist mifepristone, dexamethasone and RU24858 had no effect on NO production. The role of histone deacetylation in the glucocorticoid effect was studied by using three structurally different inhibitors of histone deacetylases (HDACs): trichostatin A, apicidin and MC1293. HDAC inhibitors reversed the effects of dexamethasone and RU24858 on iNOS expression and NO production. Stably transfected A549/8 cells containing luciferase gene under the control of human iNOS promoter were used in promoter-activity studies. iNOS promoter activity induced by IL-1beta was inhibited by dexamethasone and the inhibitory effect was reversed by HDAC inhibitor trichostatin A. The results suggest that glucocorticoids inhibit iNOS expression and NO production by a GR-mediated and GRE-independent manner through histone deacetylation and transcriptional silencing.
Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Desoximetasone; Dexamethasone; Glucocorticoids; Histone Deacetylase Inhibitors; Hydroxamic Acids; Hydroxycorticosteroids; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Peptides, Cyclic; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 17913526
DOI: 10.1016/j.pupt.2007.08.003