Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab.

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration-time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration-time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056.

Plantar Mechanical Stimulation Maintains Slow Myosin Expression in Disused Rat Soleus Muscle via NO-Dependent Signaling.

It was observed that gravitational unloading during space missions and simulated microgravity in ground-based studies leads to both transformation of slow-twitch muscle fibers into fast-twitch fibers and to the elimination of support afferentation, leading to the "switching-off" of postural muscle motor units electrical activity. In recent years, plantar mechanical stimulation (PMS) has been found to maintain the neuromuscular activity of the hindlimb muscles. Nitric oxide (NO) was shown to be one of the mediators of muscle fiber activity, which can also promote slow-type myosin expression. We hypothesized that applying PMS during rat hindlimb unloading would lead to NO production upregulation and prevention of the unloading-induced slow-to-fast fiber-type shift in rat soleus muscles. To test this hypothesis, Wistar rats were hindlimb suspended and subjected to daily PMS, and one group of PMS-subjected animals was also treated with nitric oxide synthase inhibitor (L-NAME). We discovered that PMS led to sustained NO level in soleus muscles of the suspended animals, and NOS inhibitor administration blocked this effect, as well as the positive effects of PMS on myosin I and IIa mRNA transcription and slow-to-fast fiber-type ratio during rat hindlimb unloading. The results of the study indicate that NOS activity is necessary for the PMS-mediated prevention of slow-to-fast fiber-type shift and myosin I and IIa mRNA transcription decreases during rat hindlimb unloading.

Simultaneous express immunoassay of multiple cardiac biomarkers with an automatic platform in human plasma.

C-reactive protein, cystatin C, myoglobin, and D-dimer represent the inflammatory or thromboembolic status of the patient and play important roles in early diagnostics of acute myocardial infarction. Each protein can indicate some health problems, but their simultaneous detection can be crucial for differential diagnostics. The express analysis of these proteins in a small drop of plasma was developed using magnetic beads. The suggested method is based on immunomagnetic extraction of the target analyte from plasma samples and its simultaneous labelling by fluorescent dye. Reaction time was optimized for quantification of cardiac biomarkers in the spike solutions and human plasma samples. In this paper, we developed a one-protein detection technique for each cardiac biomarker and united it to a four-protein facility using an automatic platform. The proposed technique requires only 17 µL of the human plasma and takes 14 min for four-protein measuring. The suggested technique covers concentration difference by more than two orders of magnitude and demonstrates analytical applicability by measurements of human plasma samples of 16 volunteers.