Muramyl peptides in the complex treatment of cervical intraepithelial neoplasia associated with human papillomavirus

Research objective: the use of an immunomodulator III generation with a wide range of action (muramyl peptide drug Liastenum) to increase the effectiveness of treatment of cervical intraepithelial neoplasia grade I associated with human papilloma virus (HPV) and to reduce the recurrence of cervical pathology.Materials and methods. The study included 60 women with histologically confirmed cervical intraepithelial neoplasia associated with highly oncogenic HPV. The mean age of patients was 25.92 ± 0.61 years. The first group included 30 women who received traditional treatment, the second group included 30 women who additional received Liastenum 0.002 g intramuscularly 1 time per day, 5 injections per course, after that patients took 1 tablets Liastenum twice a day for 20 days.Traditional treatment included antibiotic therapy (doxycycline monohydrate), metronidazole, nystatin in standard dosage. Patients with herpes viruses received valaciclovir 500 mg twice/day for 5 days. Evaluation of treatment efficacy was performed at 6 and 12 months with co-testing, fluid cytology, HPV quantification, and colposcopy.Results. There was a significant decrease in the exposure level of highly oncogenic HPV in the second group compared to the first: after 12 months in the first group HPV was not detected in 2 women (6.67%), and in the second group HPV was no detected in 17 women (56.67%) (p < 0.05). Improvement of the colposcopic picture occurred in 70% of patients in the second group, and in 12 (40.0%) of patients colposcopic conclusion on the Swedish scale was less than 3 points after 12 months of observation. Only 8 (26.67%) women received improvement of the colposcopic picture with a score of 3 points on the Swedish scale in the first group, which was significantly different from the second group (p < 0.05).Conclusions. Advanced therapy with muramyl peptide Liastenum in the treatment of cervix for 12 months can increase the effectiveness of HPV elimination, improves the colposcopic picture by reducing the area of cervical lesions and normalized cytological picture in 70% of patients with cervical intraepithelial neoplasia grade I.

IMMUNOLOGICAL CRITERIA FOR EFFECTIVE SYSTEMIC USE OF MURAMYL PEPTIDE IMMUNOMODULATOR IN THE TREATMENT OF PATIENTS WITH BURN INJURIES

Introduction. The problem of providing effective care to patients with burn injuries remains far from being finally solved. Due to significant immune disorders that occur against the background of thermal damage, the use of immunomodulatory drugs remains promising. Therefore, the aim of this study was to analyze the effectiveness of systemic use of the immunomodulatory drug Liastenum® in the complex treatment of patients with burn injuries. Materials and methods: The study involved 35 patients with burn injuries with the index of damage severity ranging from 30 to 60 units. Patients in the main group (n = 15) in addition to the usual treatment received an immunomodulator Liastenum®, which was administered intramuscularly at a dose of 2 mg once every 3 days (course dose — 10 mg). Treatment of patients in the comparison group (n = 20) did not involve the use of drugs with targeted immunocorrective action. Examination of patients included laboratory immunological examination of venous blood with assessment of various parts of the immune system and determination of the “Neutrophilic granulocytes form factor” indicator, which was performed on the 3rd, 14th, 21st day after the injury. The results of the study and their discussion. The obtained results allowed to confirm the ability of Liastenum® to stimulate the functional activity of neutrophilic granulocytes, restoring the phagocytic reserves of these cells, to normalize the level of lymphocytes and their individual subpopulation forms. In general, the action of the immunomodulatory drug was characterized by a balanced effect on the cellular, humoral parts of the immune system, phagocytosis. Conclusions. The effectiveness of systemic use of immunomodulatory drug Liastenum® in a comprehensive program of care for patients with burn injuries by balanced correction of immune disorders was laboratory established.

Understanding the molecular differential recognition of muramyl peptide ligands by LRR domains of human NOD receptors

Human nucleotide-binding oligomerization domain proteins, hNOD1 and hNOD2, are host intracellular receptors with C-terminal leucine-rich repeat (LRR) domains, which recognize specific bacterial peptidoglycan (PG) fragments as their ligands. The specificity of this recognition is dependent on the third amino acid of the stem peptide of the PG ligand, which is usually meso-diaminopimelic acid (mesoDAP) or l-lysine (l-Lys). Since the LRR domains of hNOD receptors had been experimentally shown to confer the PG ligand-sensing specificity, we developed three-dimensional structures of hNOD1-LRR and the hNOD2-LRR to understand the mechanism of differential recognition of muramyl peptide ligands by hNOD receptors. The hNOD1-LRR and hNOD2-LRR receptor models exhibited right-handed curved solenoid shape. The hot-spot residues experimentally proved to be critical for ligand recognition were located in the concavity of the NOD-LRR and formed the recognition site. Our molecular docking analyses and molecular electrostatic potential mapping studies explain the activation of hNOD-LRRs, in response to effective molecular interactions of PG ligands at the recognition site; and conversely, the inability of certain PG ligands to activate hNOD-LRRs, by deviations from the recognition site. Based on molecular docking studies using PG ligands, we propose few residues — G825, D826 and N850 in hNOD1-LRR and L904, G905, W931, L932 and S933 in hNOD2-LRR, evolutionarily conserved across different host species, which may play a major role in ligand recognition. Thus, our integrated experimental and computational approach elucidates the molecular basis underlying the differential recognition of PG ligands by hNOD receptors.