Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study.

BACKGROUND: NB-UVB has long been the vitiligo management pillar with capability of achieving the main treatment outcomes; repigmentation and stabilization. Its stabilizing effect in dark skin has been debatable. However, randomized controlled trials regarding NB-UVB ability to control disease activity are lacking. PURPOSE: To assess stabilizing effect of NB-UVB in comparison to systemic corticosteroids, the mainstay in vitiligo stabilization, in skin photo-types (III-V). METHODS: This is a multicenter, placebo-controlled, randomized, prospective study. Eighty patients with active nonsegmental vitiligo (NSV) (Vitiligo disease activity (VIDA) ≥2) were randomized to either NB-UVB and placebo (NB-placebo) or NB-UVB and dexamethasone oral mini-pulse (OMP) therapy (NB-OMP) for 6 months. Sixty four patients completed the study, 34 in the NB-OMP group and 30 in the NB-placebo group. Patients were evaluated fortnightly according to presence or absence of symptoms/signs of activity. RESULTS: In spite of earlier control of disease activity observed in the NB-OMP group, it was comparable in both groups by the end of the study period. Disease activity prior to therapy, but not extent, was found to influence control of activity in both groups. Thus, NB-UVB is a safe sole therapeutic tool in vitiligo management. Not only does it efficiently achieve repigmentation, but also it is a comparable stabilizing tool for systemic corticosteroids in spite of slightly delayed control. CONCLUSION: NB-UVB is the only well-established vitiligo therapy that can be used solely whenever corticosteroids are contraindicated or immune-suppression is unjustified. Nonetheless, its combination with corticosteroids expedites response and improves compliance.

Brucine-Loaded Ethosomal Gel: Design, Optimization, and Anti-inflammatory Activity.

Brucine, one of the natural medications obtained from Nux vomica seeds, is used as an anti-inflammatory drug. Several investigations were performed to overcome its drawbacks, which will affect significantly its pharmaceutical formulation. The goal of the current investigation was to design, optimize, and evaluate the anti-inflammatory performance of BRU ethosomal gel. Brucineethosomal formulations were prepared using thin film hydration method and optimized by central composite design approach using three independent variables (lecithin concentration, cholesterol concentration, and ethanol percentage) and three response variables (vesicular size, encapsulation efficiency, and skin permeation). The optimized formulation was examined for its stability and then incorporated into HPMC gel to get BRU ethosomal gel. The obtained BRU-loaded ethosomal gel was evaluated for its physical properties, in vitro release, and ex vivo permeation and skin irritation. Finally, carrageenan-induced rat hind paw edema test was adopted for the anti-inflammatory activity. The developed BRU ethosomal gel exhibited good physical characteristics comparable with the conventional developed BRU gel. In vitro release of BRU from ethosomal gel was effectively extended for 6 h. Permeation of BRU from ethosomes was significantly higher than all formulations (p < 0.05), since it recorded steady state transdermal flux value 0.548 ± 0.03 µg/cm2 h with enhancement ratio 2.73 ± 0.23. Eventually, BRU ethosomal gel exhibited potent anti-inflammatory activity as manifested by a significant decrease in rat hind paw inflammation following 24 h. In conclusion, the study emphasized the prospective of ethosomal gel as a fortunate carrier for intensifying the anti-inflammatory effect of Brucine.

Olive oil polyphenols extracts inhibit inflammatory markers in J774A.1 murine macrophages and scavenge free radicals.

Here we evaluate the olive oil antiradical and anti-inflammatory potential through its polyphenols extracts and examine the influence of olive maturity on olive oil quality properties, polyphenols composition and biological potentials. Samples have been obtained from minor Tunisian olive cultivars (Chemchali, Fouji and Zarrazi) at different maturity indices. Principal quality properties were evaluated and polyphenols analysis was carried out by Folin Ciocalteu reagent and HPLC-UV-MS. Antiradical activity was examined by DPPH and FRAP scavenging assays while J774A.1 murine macrophages were used to evaluate anti-inflammatory potential by analyzing NO production with Griess reagent method and iNOS and COX-2 expression by cytofluorimetric analysis. Our results revealed that quality characteristics, total phenol content, as well as phenolic compound concentrations were significantly affected by the olive maturity levels. On the other hand, the polyphenols extracts showed an interesting radical scavenging capacity and a potential ability to inhibit inflammatory markers at 90% for NO release and 75% for iNOS expression. Thus, our study establishes that olive oil through its polyphenols extracts has a substantial antiradical and anti-inflammatory potential. Likewise a lot of attention should be attributed to olive ripening level in order to decide the optimum harvesting time.

Silymarin-loaded Eudragit(®) RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats.

UNLABELLED: Some nano-formulations of silymarin (SM), a drug commonly used for liver diseases, were developed to overcome its poor solubility and poor bioavailability; antifibrotic effect of these formulations has not been tested yet. In this study we aimed to formulate and evaluate silymarin-loaded Eudragit(®) RS100 nanoparticles (SMnps) and to test the capability of SMnps to reverse an established fibrosis model. SMnps were prepared by solvent evaporation and nano-precipitation techniques. The influence of drug:polymer ratio, concentration of surfactant in the aqueous phase on particle size, drug entrapment efficiency (EE) % and in vitro drug releases were investigated. For in vivo evaluation, bile duct ligated (BDL)-rats were treated with either SM or SMnps every other day (125mg/kg) orally for 3 weeks started 3 weeks after BDL. Liver function tests, oxidative stress and fibrosis/fibrogenesis process were evaluated using biochemical and histopathological techniques. The formulation No (F4) of SMnps showed an average particle size of 632.28±12.15nm, a drug EE% of 89.47±1.65% and released the drug in a prolonged manner over 24h. The prepared SMnps were nearly spherical with smooth surfaces. In BDL-rats, treatments with either SM or SMnps corrected liver function and oxidative stress. Only SMnps was able to reverse the induced fibrosis; SMnps significantly decreased serum tumor necrosis factor- α (TNF-α), serum transforming growth factor- ß1 (TGF-ß1), hepatic hydroxyproline and downregulated the hepatic expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and cytokeratin-19 (CK-19), whilst increased hepatic hepatocytes growth factor (HGF) and upregulated the hepatic expression of matrix metalloproteinase-2 (MMP-2) and increased MMP-2/TIMP-1 ratio at mRNA level. Livers of rats treated with SMnps showed very little collagen in ECM and restored hepatic architecture as compared to either BDL rats or rats treated with SM. CONCLUSION: Formulation of silymarin as nanoparticles improved its ability to resolve cholestasis-induced liver fibrosis by restoring hepatic regenerative capabilities. Therefore, formulation of SMnps may represent a step forward in the field of anti-fibrotic drug development.