Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study.

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.

Rational Choice of Reinforcement of Reinforced Concrete Frame Corners Subjected to Opening Bending Moment.

This paper discusses a choice of the most rational reinforcement details for frame corners subjected to opening bending moment. Frame corners formed from elements of both the same and different cross section heights are considered. The case of corners formed of elements of different cross section is not considered in Eurocode 2 and is very rarely described in handbooks. Several reinforcement details with both the same and different cross section heights are presented. The authors introduce a new reinforcement detail for the different cross section heights. The considered details are comprised of the primary reinforcement in the form of straight bars and loops and the additional reinforcement in the form of diagonal bars or stirrups or a combination of both diagonal stirrups and bars. Two methods of static analysis, strut-and-tie method (S&T) and finite element method (FEM), are used in the research. FEM calculations are performed with Abaqus software using the Concrete Damaged Plasticity model (CDP) for concrete and the classical metal plasticity model for reinforcing steel. The crucial CDP parameters, relaxation time and dilatation angle, were calibrated in numerical tests in Abaqus. The analysis of results from the S&T and FE methods allowed for the determination of the most rational reinforcement details.

Selected Concrete Models Studied Using Willam's Test.

Willam's test is a quick numerical benchmark in tension-shear regime, which can be used to verify inelastic (quasi-brittle) material models at the point level. Its sequence consists of two separate steps: uniaxial tension accompanied with contraction-until the tensile strength is attained; and next for softening (cracking) of the material-tension in two directions together with shear. A rotation of axes of principal strains and principal stresses is provoked in the second stage. That kind of process occurs during the analysis of real concrete structures, so a correct response of the material model at the point level is needed. Some familiar concrete models are selected to perform Willam's test in the paper: concrete damaged plasticity and concrete smeared cracking-distributed in the commercial ABAQUS software, scalar damage with coupling to plasticity and isotropic damage-both implemented in the FEAP package. After a brief review of the theory, computations for each model are discussed. Passing or failing Willam's test by the above models is concluded based on their results, indicating restrictions of their use for finite element computations of concrete structures with predominant mixed-mode fracture.

The Evaluation of Vitiligous lesions Repigmentation after the Administration of Atorvastatin calcium salt and Simvastatin-acid sodium salt in patients with active vitiligo (EVRAAS), a pilot study: study protocol for a randomized controlled trial.

BACKGROUND: Vitiligo is a chronic skin disorder presenting with depigmentation, the pathogenesis of which is complex but the autoimmune theory is now preferred. Multiple immunologic processes, including stimulation of the T-helper (Th)1 response, formation of autoreactive melanocyte-specific CD8+ T lymphocytes, a decrease in the blood concentration of T regulatory (Treg) cells, and an increase in interleukin (IL)-17 and interferon (IFN) concentration, have been shown to contribute to vitiligo progression and maintenance. The aim of this study is to evaluate the influence of simvastatin and atorvastatin on vitiligous lesions in patients with nonsegmental vitiligo (NSV). According to available data, statins act through several immunological pathways, potentially reversing undesirable phenomena underlying autoimmune vitiligo pathogenesis. METHODS/DESIGN: A study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of at least 24 active NSV patients presenting with vitiligous lesions on both upper and lower limbs. The clinical effects of ointments containing 1% simvastatin-acid sodium salt or 1% atorvastatin calcium salt applied on a preselected limb will be assessed in comparison with vehicle ointment applied on the opposite limb. All study participants will undergo clinical evaluation using body surface area (BSA) and Vitiligo Area Scoring Index (VASI) scales at baseline and at weeks 4, 8, and 12 time points. A precise assessment of skin lesions will be performed using photographic documentation obtained during each study visit and processed with NIS-Elements software. DISCUSSION: Currently available vitiligo topical therapeutic approaches including calcineurin inhibitors and corticosteroids remain poorly effective and are associated with either relatively high cost or potentially dangerous adverse effects. The clinical application of orally administrated statins, widely used as systemic cholesterol-lowering agents, in vitiligous patients has only been tested in two clinical trials; however, data on their potential usefulness is scarce. Moreover, due to a high risk of clinically significant toxicity, topical administration was recommended by researchers. This study is the first to evaluate safety and efficacy of the topical use of statins in patients presenting with NSV. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03247400 . Registered on 05 August 2017.