Обоснование выбора электродвигателя и схемы его включения для системы точного поддержания скорости

Рассматривается применение в системах точного поддержания скорости различных синхронных электродвигателей. В результате сравнения рекомендовано применение в таких системах конденсаторного синхронного реактивного двигателя с трехфазными обмотками статора. Это позволяет упростить и удешевить систему точного электропривода и повысить ее надежность

Biomarker analysis from the phase 2b randomized placebo-controlled trial of riociguat in early diffuse cutaneous systemic sclerosis

OBJECTIVE To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION Clinicaltrials.gov, NCT02283762

Differentiation plasticity of stromal vascular fraction cells towards adipose tissue and endothelial structures

Recent research findings postulate that adipocytes and endothelial cells (ECs) may share a common progenitor. However, the interlinking pathways between adipose tissue and endo-thelium, and the differentiation potential of cells to convert from one tissue into the other via progenitor cells, have not been elucidated so far and are therefore the focus of this thesis. Stromal vascular fraction (SVF) cells were isolated from liposuction aspirates or excised adi-pose tissue and separated into CD31+ and CD31- populations by magnet-assisted cell sorting. Differentiation to fat tissue was induced in both CD31 fractions. Differentiation was assayed enzymatically and by cell counting. Maturation to endothelium was performed with vascular endothelial growth factor, insulin like growth factor-1 plus 2% FCS and confirmed by flow cytometry and tube formation assays on Matrigel™. The results presented here show that the SVF contains a CD31-, S100+ cell type which can differentiate into adipocytes and EC. The SVF also comprises CD31+ cells that, although they have an endothelial phenotype, can be converted into mature adipocytes. These findings demonstrate the potency of SVF cells to perform both adipogenic and endothelial differentiation. Further, they reveal the plasticity of mature cells of mesenchymal origin to undergo conversion from endothelium to adipose tis-sue and vice versa

Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study

Introduction: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). Methods: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. Results: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose–response signal with eliapixant was detected for the primary endpoint (all dose–response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43–51 (57–65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1–16% (n = 1–13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. Conclusion: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. Trial Registration: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020

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plasticity of stromal vascular fraction cells towards adipose tissu

Riociguat in patients with early diffuse cutaneous systemic sclerosis (RISE-SSc): open-label, long-term extension of a phase 2b, randomised, placebo-controlled trial

Background The phase 2b Riociguat Safety and Efficacy in Patients with Diffuse Cutaneous Systemic Sclerosis (RISE-SSc) trial investigated riociguat versus placebo in early diffuse cutaneous systemic sclerosis. The long-term extension evaluated safety and exploratory treatment effects for an additional year. Methods Patients were enrolled to RISE-SSc between Jan 15, 2015, and Dec 8, 2016. Those who completed the 52-week, randomised, parallel-group, placebo-controlled, double-blind phase were eligible for the long-term extension. Patients originally assigned to riociguat continued therapy (riociguat–riociguat group). Those originally assigned to placebo were switched to riociguat (placebo–riociguat group), adjusted up to 2·5 mg three times daily in a 10-week, double-blind dose-adjustment phase, followed by an open-label phase. Statistical analyses were descriptive. Safety including adverse events and serious adverse events was assessed in the long-term safety analysis set (all patients randomly assigned and treated with study medication in the double-blind phase who continued study medication in the long-term extension). The RISE-SSc trial is registered with ClinicalTrials.gov, NCT02283762. Findings In total, 87 (72%) of 121 patients in the main RISE-SSc study entered the long-term extension (riociguat–riociguat, n=42; placebo–riociguat, n=45). 65 (75%) of 87 patients were women, 22 (25%) were men, and 62 (71%) were White. Overall, 82 (94%) of 87 patients in the long-term extension had an adverse event; most (66 [76%] of 87) were of mild to moderate severity, with no increase in pulmonary-related serious adverse events in patients with interstitial lung disease. Interpretation No new safety signals were observed with long-term riociguat in patients with early diffuse cutaneous systemic sclerosis. Study limitations include the absence of a comparator group in this open-label extension study. Funding Bayer and Merck Sharp & Dohme