Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse.

Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mdx mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mdx mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1ß partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mdx mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mdx mice, and CCL2, HSPA1A, TNF-α and IL-1ß in taurine-treated mdx mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mdx mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mdx mice and, for the first time, demonstrated similar and differential effects of ectoine.

Effectiveness of a Mindfulness-Based Mobile Application for the Treatment of Depression in Ambulatory Care: Protocol for a Randomized Controlled Trial.

BACKGROUND: Patients with major depressive disorder (MDD) often experience relapses despite regular treatment with pharmacotherapy and psychotherapy. Further, long waiting lists and more demand than treatment capacity characterize ambulatory settings. Mindfulness-based interventions proved to be effective in relapse prevention in MDD. Next, mindfulness-based interventions in the form of free mobile applications can be an effective augmentation of the treatment as usual and can fill a gap in ambulatory care. OBJECTIVE: Given this background, the aim of this randomized controlled study is to assess the effectiveness of additional MBI via a mobile app on the symptom severity and stress levels, compared to treatment as usual. METHODS: A total of 140 individuals with MDD will be randomly allocated to the intervention or control condition. The intervention consists of the daily use of the mindfulness mobile application Headspace for thirty days (up to 10 minutes a day). The control condition will be treatment as usual. At baseline and four weeks later, the following key outcome dimensions will be assessed: self-rated (Beck Depression Inventory) and experts' rated symptoms of MDD (Hamilton Depression Rating Scale); secondary outcome variables will be blood pressure, heart rate, and respiratory rate and changes in tobacco and alcohol consumption and medication as a proxy of perceived stress. RESULTS: This study was funded in February 2021 and approved by the institutional review board on April 15, 2021, and it started in May 2021. As of December 2021, we enrolled 30 participants. The findings are expected to be published in spring 2023. CONCLUSIONS: We hypothesize that compared to the control conditions, individuals with MDD of the mobile app-condition will have both lower self- and experts' rated symptoms of MDD and more favorable stress-related levels. While the risk for medical events is low, the immediate benefit for participants could be a decrease in symptom severity and reduction of the stress level. TRIAL REGISTRATION: Clinical Trials.gov NCT05060393; https://clinicaltrials.gov/ct2/show/NCT05060393. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33423.

In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.