Long-term use of etelcalcetide for the treatment of secondary hyperparathyroidism in patients undergoing hemodialysis for end-stage renal failure: a real-life retrospective observational study.

BACKGROUND: Patients with end-stage renal failure (ESRD) or dialysis frequently suffer from secondary hyperparathyroidism (sHPTH), a severe complication of mineral metabolism disorders. The calcimimetic etelcalcetide has been approved and shown efficacy in randomized controlled trials, however, data are limited from real-life studies. This study aimed to evaluate the long-term use etelcalcetide for the treatment of sHPTH (PTH > 600 pg/mL) in patients undergoing extracorporeal hemodialysis for ESRD for at least 2 years. METHODS: In 45 patients, we administered etelcalcetide for the treatment of sHPTH (PTH > 600 pg/mL); One group of patients (control group, Group A; N = 26) were previously treated with intravenous vitamin D analogues only (paricalcitol 5 µg/ml, three times/week) and then treated with etelcalcetide and a second group of patients already on cinacalcet therapy for at least six months in combination with iv paricalcitol were switched to etelcalcetide (Group B, N = 19). RESULTS: PTH levels decreased over time in both groups of patients, with higher values for patients previously treated with cinacalcet (Group B) compared to Group A for the entire study duration even if the final value of the two groups was comparable. After 12 months, the percentage of subjects who had PTH concentrations within the targets recommended by KDIGO guidelines was 87% in Group A and 58% in Group B. In seven patients, despite a parathyroid gland volume > 1000 mm3, an adequate response in the reduction of PTH was obtained. CONCLUSION: Findings from this study demonstrate that the efficacy of etelcalcetide is maintained over the long term.

Mucosal Immunity After Novel COVID-19 Infection - Virus-Induced Immunosuppression: Preliminary Study.

In recovered COVID-19 patients, the state of mucosal immunity remains understudied. Cytological, functional, and metabolic characteristics of neutrophils and the interleukin status will help to correctly assess the need for immunorehabilitation measures. The study objective is to assess the state of mucosal immunity after COVID-19. A comprehensive study of mucosal immunity included the assessment of nasal mucosal neutrophils with the monitoring of destructive and apoptotic changes as well as examination of the functional and metabolic activity of neutrophils entering the nasal secretions. Phagocytic activity was assessed using microbial suspension of Staphylococcus aureus, as well as intracellular oxygen-dependent biocidity, the functions of capturing, absorbing, and killing pathogens. Study of the secretory component included assessment of interleukin levels (TNF-α, IL-10, IFN-γ) and the content of sCD95 (sAPO-1/FAS), membrane marker of apoptosis, in the nasal secretions. Cell wall neutrophils in recovered COVID-19 patients show enhanced destructive and apoptotic processes within the cells. Functional disorders due to inhibited phagocytosis of autoflora are recorded. Functionally defective cells are brought into the nasal secretions; they demonstrate severely inhibited oxygen-dependent biocidity, rapid depletion of reserves, incomplete phagocytosis, and limited ability to capture pathogens, which can contribute to the growth of various pathogenic viruses and bacteria. In the nasal secretions, the concentration of sCD95 (sAPO-1/FAS), the membrane marker of apoptosis, is increased. Elevated level of pro- and anti-inflammatory cytokines (TNF-α, IL-10) downregulates IFN-γ, thus directly contributing to the formation of functionally defective neutrophils. Compensatory increase in the IL-10 anti-inflammatory cytokine under the influence of SARS-CoV-2 virus proteins downregulates IFN-γ and is a cofactor of depression of intracellular biocidity of neutrophils. An increased level of the TNF-α pro-inflammatory cytokine increases apoptotic and destructive changes in neutrophils entering the nasal secretion. Virus-induced, functional, and metabolic impairment of neutrophils of the mucosal immunity system develop in recovered COVID-19 patients, thus providing a scientific rationale for immunomodulatory therapy.

Whole-Genome Sequencing of Vibrio cholerae O1 El Tor Strains Isolated in Ukraine (2011) and Russia (2014).

Here, we present the draft whole-genome sequence of Vibrio cholerae O1 El Tor strains 76 and M3265/80, isolated in Mariupol, Ukraine, and Moscow, Russia. The presence of various mutations detected in virulence-associated mobile elements indicates high genetic similarity of the strains reported here with new highly virulent variants of the cholera agent V. cholerae.

Co-expression of the Thermotoga neapolitana aglB gene with an upstream 3'-coding fragment of the malG gene improves enzymatic characteristics of recombinant AglB cyclomaltodextrinase.

A cluster of Thermotoga neapolitana genes participating in starch degradation includes the malG gene of sugar transport protein and the aglB gene of cyclomaltodextrinase. The start and stop codons of these genes share a common overlapping sequence, aTGAtg. Here, we compared properties of expression products of three different constructs with aglB from T. neapolitana. The first expression vector contained the aglB gene linked to an upstream 90-bp 3'-terminal region of the malG gene with the stop codon overlapping with the start codon of aglB. The second construct included the isolated coding sequence of aglB with two tandem potential start codons. The expression product of this construct in Escherichia coli had two tandem Met residues at its N terminus and was characterized by low thermostability and high tendency to aggregate. In contrast, co-expression of aglB and the 3'-terminal region of malG (the first construct) resulted in AglB with only one N-terminal Met residue and a much higher specific activity of cyclomaltodextrinase. Moreover, the enzyme expressed by such a construct was more thermostable and less prone to aggregation. The third construct was the same as the second one except that it contained only one ATG start codon. The product of its expression had kinetic and other properties similar to those of the enzyme with only one N-terminal Met residue.

Molecular cloning and characterization of an endo-1,3-beta-D-glucanase from the mollusk Spisula sachalinensis.

cDNA encoding the endo-1,3-beta-d-glucanase from Spisula sachalinensis (LIV) was amplified by PCR using oligonucleotides deduced from the N-terminal end peptide sequence. Predicted enzyme structure consists of 444 amino acids with a signal sequence. The mature enzyme has 316 amino acids and its deduced amino acid sequence coincides completely with the N-terminal end (38 amino acids) of the beta-1,3-glucanase (LIV) isolated from the mollusk. The enzyme sequence from Val 121 to Met 441 reveals closest homology with Pacifastacus leniusculus lipopolysaccharide- and beta-1,3-glucan-binding protein and with coelomic cytolytic factors from Lumbricus terrestris. The mollusk glucanase also shows 36% identity and 56% similarity with beta-1,3-glucanase of the sea urchin Strongylocentrotus purpuratus. It is generally considered that invertebrate glucanase-like proteins containing the bacterial glucanase motif have evolved from an ancient beta-1,3-glucanase gene, but most of them lost their glucanase activity in the course of evolution and retained only the glucan-binding activity. A more detailed evaluation of the protein folding elicited very interesting relationships between the active site of LIV and other enzymes, which hydrolyze native glucans.