[Improving the effectiveness of local anesthesia in patients with arterial hypertension in the provision of emergency dental care]. / Povyshenie effektivnosti mestnogo obezbolivaniya u patsientov s arterial'noi gipertenziei pri okazanii neotlozhnoi stomatologicheskoi pomoshchi.

THE AIM OF THE STUDY: Was to evaluate the use of Ketorol Express as a preventive analgesia to increase the effectiveness of local anesthesia in providing emergency dental care to patients with arterial hypertension. MATERIALS AND METHODS: The study was conducted on the basis of the state autonomous healthcare institution of the Moscow region «Royal Dental Clinic¼ with the participation of 83 people. The patients were divided into two groups. In group 1, Ketorol Express was prescribed as a preventive analgesia in a dosage of 20 mg before local anesthesia. Patients of group 2 underwent dental interventions without the use of preventive analgesia. A 3% solution of mepivacaine was used as a local analgesic solution. For a subjective assessment of the effectiveness of anesthesia, use a visual analog scale. All patients had their blood pressure and heart rate measured before and after the interventions and hemodynamic parameters were continuously monitored during emergency dental care. RESULTS: In group 1, the effectiveness of combined anesthesia with the infiltration method of local anesthetic administration was 93±1.17%, according to the patient, 94±1.47%, according to the doctor, with the conductive method of anesthesia at the mandibular orifice - according to the patient it was 91±1.01%, according to the doctor 92± 1.36%. In group 2, when providing emergency dental care with the infiltration method of administration of 3% mepivacaine the anesthesia was effective in 80±1.97% of cases according to the patient and in 80±1.17% of cases according to the doctor, with the conductive method of anesthesia at the mandibular orifice, the effectiveness of anesthesia according to the patient was 82±1.11%, according to the doctor 85±1.23%. CONCLUSION: The results of the study demonstrated a statistically significant increase in the effectiveness of local anesthesia performed with a 3% solution of mepivacaine in patients with arterial hypertension due to the use of preventive analgesia with Ketorol Express at a dosage of 20 mg (2 tablets of 10 mg) in emergency dental care with registration and analysis of changes in hemodynamic parameters.

Methionine gamma lyase fused with S3 domain VGF forms octamers and adheres to tumor cells via binding to EGFR.

Methods for targeting enzymes exhibiting anticancer properties, such as methionine γ-lyase (MGL), have not yet been sufficiently developed. Here, we present the data describing the physico-chemical properties and cytotoxic effect of fusion protein MGL-S3 - MGL from Clostridium sporogenes translationally fused to S3 domain of the viral growth factor of smallpox. MGL-S3 has methioninase activity comparable to native MGL. In solution, MGL-S3 protein primarily forms octamers, whereas native MGL, on the contrary, usually forms tetramers. MGL-S3 binds to the surface of the neuroblastoma SH-SY5Y and epidermoid carcinoma A431 cells and, unlike native MGL, remains there and retains its cytotoxic effect after media removal. In HEK293T cells lacking EGFRs, no adhesion was recorded. Confocal fluorescence microscopy confirms the preferential adhesion of MGL-S3 to tumor cells, while it avoids getting into lysosomes. Both MGL and MGL-S3 arrest cell cycle of SH-SY5Y cells mainly in the G1 phase, while only MGL-S3 retains this ability after washing the cells.

Prospects for the Use of Marine Sulfated Fucose-Rich Polysaccharides in Treatment and Prevention of COVID-19 and Post-COVID-19 Syndrome.

Symptoms of the new coronavirus infection that appeared in 2019 (COVID-19) range from low fever and fatigue to acute pneumonia and multiple organ failure. The clinical picture of COVID-19 is heterogeneous and involves most physiological systems; therefore, drugs with a wide spectrum of mechanism of action are required. The choice of the treatment strategy for post-COVID-19 syndrome is still a challenge to be resolved. Polysaccharides with a high fucose content derived from seaweed and marine animals can form the basis for the subsequent development of promising agents for the treatment of COVID-19 and post-COVID-19 syndrome. This class of biopolymers is characterized by a variety of biological activities, including antiviral, antithrombotic, anticoagulant, hemo-stimulating, anti-inflammatory and immune-regulatory. Low molecular weight derivatives of these polysaccharides, as well as synthetic oligosaccharides with a sufficient amount and sulfation type may be considered as the most promising compounds due to their better bioavailability, which undoubtedly increases their therapeutic potential.

Erratum to: Prospects for the Use of Marine Sulfated Fucose-Rich Polysaccharides in Treatment and Prevention of COVID-19 and Post-COVID-19 Syndrome.

[This corrects the article DOI: 10.1134/S1068162022060152.].

[Comparative analysis of 2% and 4% articaine solution efficacy and safety for the local anesthesia]. / Sravnitel'nyi analiz primeneniya 2% i 4% rastvora artikaina pri in"ektsionnoi mestnoi anestezii.

AIM: To determine the functional diagnostics criteria for predicting the effectiveness of using 2% and 4% solutions articaine without vasoconstrictor and with epinephrine content of 1:200.000. MATERIAL AND METHODS: The study involved 357 patients (193 women and 164 men) aged 20 to 35 years. with the presence of intact single-rooted and multi-rooted teeth without periodontal pathology without pronounced general somatic pathology, and with a low level of situational anxiety according to the Spielberger-Khanin scale. All the patients received injection anesthesia by the infiltration method of 2% and 4% articaine solution without vasoconstrictor or with epinephrine concentration of 1:200.000. The effectiveness of local anesthesia was assessed by recording functional parameters (electrosensitivity threshold test and hemomicrocirculation) of the pulp of intact single-root and multi-root teeth before anesthesia, 5, 10, 15, 30, and 60 minutes after local anesthesia. The safety of the anesthesia was determined by continuous monitoring of the patient's hemodynamic parameters: blood pressure, heart rate, blood oxygen saturation before anesthesia and within 60 minutes after. RESULTS: Articaine solution 2% with epinephrine concentration of 1:200.000 used for infiltration or modified periodontal anesthesia resulted in pulp electrosensitivity threshold growth by 95.93% and 93.58%, respectively. There were no statistically significant differences in hemodynamic values between both study groups. CONCLUSION: Analysis of the data obtained showed the effectiveness and safe anesthesia with drugs based on 2% articaine with an epinephrine concentration of 1:200.000.

Combination of Muramylpeptides from Gram-Negative Bacteria Corrects Cyclophosphamide-Induced Disorders of Hematopoiesis and Spleen Cell Composition in Mice with B16 Melanoma.

We studied the effect of a combination of three muramylpeptides from gram-negative bacteria (Polymuramyl) on hematological parameters, morphology of the spleen, and serum cytokine level in mice with B16 melanoma treated with cyclophosphamide. Intraperitoneal administration of cyclophosphamide to tumor-bearing animals sharply reduced the number of leukocytes, especially neutrophils, in the blood and depleted the cellular composition of the spleen white pulp. Subsequent three daily intramuscular injections of Polymuramyl in doses of 70 and 860 ng/mouse for 3 days, as well as subcutaneous injection of the reference drug filgrastim (granulocytic CSF) in a dose of 12 µg/mouse partially corrected hematopoietic disorders and restored the cellular composition of the spleen. Granulocytic CSF more effectively replenished the content of mature neutrophils in the blood, while Polymuramyl restored the content of stab neutrophils. In contrast to granulocytic CSF, administration of Polymuramyl was followed by an increase in the level of granulocyte-macrophage CSF and a tendency to an increase in the serum content of IL-6, which indicates the involvement of these cytokines in the hematopoietic activity of Polymuramyl.

Antibacterial Activity of Hybrid Polymeric Scaffold for Reconstruction of Tubular Bone Defects.

We studied antibacterial activity of a hybrid polymeric construction consisting of continuous and porous layers of ultrahigh-molecular-weight polyethylene reinforced by titanium. Experimental samples were impregnated with amoxycillin in subcritical Freon R22. The contact of bacterial culture with hybrid polymeric constructions saturated with amoxycillin suppressed the growth of microorganisms and the formation of their colonies. These results attest to the presence of a bactericidal effect of hybrid scaffold samples impregnated with an antibacterial component.

A Combination of Muramylpeptides from Gram-Negative Bacteria Corrects Hematological and Immunological Disorders Induced by Cyclophosphamide.

We have studied the effect of a combination of three natural muramylpeptides containing a meso-diaminopimelic acid residue (polyramyl) on the subpopulations of circulating T cells, spleen morphology, and leukocyte level in the blood of C57Bl/6 mice with cyclophosphamideinduced immunosuppression. Intraperitoneal injections of cyclophosphamide in a dose of 100 mg/kg on days 1, 3, 5, and 7 of the experiment reduced leukocyte count and the relative number of CD4+ T cells in the blood, and also depleted the cellular composition of splenic white pulp on day 10. Subcutaneous injections of polyramyl in a dose of 200 µg/mouse on days 8 and 9 practically completely restored blood leukocytes count and morphology of the splenic white pulp. Moreover, administration of polyramyl induced marked tendency to increase in the relative number of CD4+ T cells and CD4/CD8 ratio in mice with cyclophosphamideinduced immunosuppression.

Methionine Gamma Lyase from Clostridium sporogenes Increases the Anticancer Efficacy of Doxorubicin on A549 Cancer Cells In Vitro and Human Cancer Xenografts.

The anticancer efficacy of methionine γ-lyase (MGL) from Clostridium sporogenes (C. sporogenes) is described. MGL was active against cancer cells in vitro and in vivo. Doxorubicin (DOX) and MGL were more effective on A549 human lung-cancer growth inhibition than either agent alone in vitro and in vivo.

Multilayer porous UHMWPE scaffolds for bone defects replacement.

Reconstruction of the structural integrity of the damaged bone tissue is an urgent problem. UHMWPE may be potentially used for the manufacture of porous implants simulating as closely as possible the porous cancellous bone tissue. But the extremely high molecular weight of the polymer does not allow using traditional methods of foaming. Porous and multilayer UHMWPE scaffolds with nonporous bulk layer and porous layer that mimics cancellous bone architecture were obtained by solid-state mixing, thermopressing and washing in subcritical water. Structural and mechanical properties of the samples were studied. Porous UHMWPE samples were also studied in vitro and in vivo. The pores of UHMWPE scaffold are open and interconnected. Volume porosity of the obtained samples was 79±2%; the pore size range was 80-700µm. Strong connection of the two layers in multilayer UHMWPE scaffolds was observed with decreased number of fusion defects. Functionality of implants based on multilayer UHMWPE scaffolds is provided by the fixation of scaffolds in the bone defect through ingrowths of the connective tissue into the pores, which ensures the maintenance of the animals' mobility.

Influence of fucoidans and their derivatives on antitumor and phagocytic activity of human blood leucocytes.

The immunotropic activity of structurally different fucoidans and their derivatives towards isolated immune blood cells, effectors of innate immune system, was studied. The most potent effect was observed for high molecular weight fucoidan CF from the alga Chordaria flagelliformis, whose backbone is built of (1→3)-linked units of α-L-fucopyranose, and branches included residues of α-D-glucuronic acid and α-L-fucofuranose. This compound at the concentration of 0.05 mg/ml potentiated phagocytosis of Saccharomyces cerevisiae and Lactobacillus acidophilus by neutrophils, increasing relative quantity of phagocytes as well as their effectiveness. Along with this, 14% increase in the concentration of membrane-bound integrin CD11c molecules was observed. The systemic effect of CF at the dose of 0.01 mg/mouse i.p. led to potentiation of cytotoxic activity of spleen mononuclear leucocytes towards melanoma cells of line B16 by 1.9-fold and towards chronic myelogenous leukemia cells of line K-562 by 1.7-fold. These results indicate that fucoidan CF can stimulate anti-infective and antitumor activity of effectors of the innate immune system via CD11c integrins.

[PROSPECTIVE SYNTHETIC MATRICES FOR THE RECONSTRUCTION OF TRACHEAL DEFECTS IN CANCER PATIENTS].

A replacement of major defects of the trachea remains a challenge despite numerous attempts to use for this purpose various options of autologous and allogeneic implants as well as synthetic matrixes. The most prospective direction is to create tracheal matrixes based on biocompatible porous or fibrous materials that mimic native tissues and provide the proliferation of multipotent cells. This review summarizes current data regarding the development of experimental research and clinical testing of biocompatible tracheal matrixes, which were created using innovative technologies.

UHMWPE-based nanocomposite as a material for damaged cartilage replacement.

In the present work dispersion-strengthened nanocomposites based on ultra-high molecular weight polyethylene (UHMWPE) after mechanical activation were studied. Mechanical activation was performed for hardening of the boundaries between the polymer particles, reducing the fusion defects and increasing of wear-resistance. Three types of samples were prepared: UHMWPE, UHMWPE/Al2O3 nanocomposite and UHMWPE/Al2O3 nanocomposite after mechanical activation. UHMWPE/Al2O3 nanocomposites prepared with mechanical activation show the best mechanical properties in compression and higher wear-resistance. UHMWPE/Al2O3 nanocomposites prepared with mechanical activation were chosen for in vivo study by orthotopical transplantation in rats. Animals' activity has been being monitored for 60days after surgery. No signs of inflammation, cellular infiltration, destruction of material or bone-cartilage defect were found. Implanted sample has not changed its position of implantation, there were no any shifts. Obtained data shows that UHMWPE-based nanocomposite is a promising material for creating bioimplants for cartilage defect replacement.

Cloning, expression and characterization of the recombinant Yersinia pseudotuberculosis L-asparaginase.

We have cloned ansB (YPTB1411) gene from Yersinia pseudotuberculosis Q66CJ2 and constructed stable inducible expression system that overproduce L-asparaginase from Y. pseudotuberculosis (YpA) in Escherichiacoli BL21 (DE3) cells. For purification of YpA we used Q-Sepharose and DEAE-Toyopearl column chromatography. We examined kinetics of the enzyme reaction, catalytic activity as a function of pH, temperature and ionic strength, thermostability and other enzyme properties. Biochemical properties of YpA are similar with those of E. coli type II L-asparaginase. K(m) for L-asparagine is 17 ± 0.9 µM and pI 5.4 ± 0.3. Enzyme demonstrates maximum activity at pH 8.0 and 60 °C. YpA L-glutaminase activity is relatively low and more than 15 times less than specific activity towards L-asn. We evaluated also the antiproliferative effect of YpA in vitro and in vivo with E. colil-asparaginase (EcA) as the reference substance at similar conditions.

Dynamics of elimination of bacterial endotoxins and cytokines from the blood of tumor patients with sepsis in hemoperfusion using carbon adsorbents.

We studied the effects of carbon adsorbent hemoperfusion on the dynamics of LPS and cytokine concentrations in the blood of cancer patients with sepsis and septic shock. In addition, hemadsorbent washout fluid specimens after hemoperfusion were analyzed. A significant (3-fold) reduction of blood LPS levels after hemoperfusion was found, while shifts in free cytokine levels in the sera were negligible. At the same time, hemadsorbents used in the study effectively eliminated some free cytokines (IL-6, -8, -12, IFN-γ, TNF-α) from the blood.

Optimization of a method for preparation and repopulation of the tracheal matrix for allogenic transplantation.

A method for decellularization of the trachea for subsequent repopulation with allogenic MSC was optimized. Tracheas from C57BL/6 mice were devitalized and repopulated with MSC from BALB/c mice. The tracheal matrix with devitalized mucosa and intact cartilaginous structure, fit for repopulation with allogenic MSC, was obtained by chemical treatment with NaClO4. This approach seemed to be promising for transplantation of allogenic trachea.

Possibility of microorganism elimination from the blood using modified coal hemosorbents.

We studied the possibility of using coal hemosorbents for elimination gram-positive and gram-negative microorganisms from the blood. After hemosorption, the number of S. aureus and K. pneumoniae pneumoniae colony-forming units significantly decreased. The obtained results indicate that coal sorbents can bind and probably eliminate gram-positive and gram-negative bacteria from the blood.

Selective cytokine-inducing effects of low dose Echinacea.

Echinacea purpurea is a widely used plant immunomodulator with a selective immunomodulatory effect depending on the dilution of the initial preparation. In low doses, it causes selective induction of pro- and anti-inflammatory cytokines. The results recommend this preparation in a wide range of concentrations for adequate correction of the immune system work aimed at restoring the Th1/Th2 balance in various diseases.

Identification of serpin (alpha-1-antitrypsin) as serum growth inhibitory factor in murine ehrlich carcinoma by proteomics.

It is well established that serum factors play a role in relapse of tumor diseases after removal of the primary tumor. The molecular nature of these factors and their mechanism of action remain unknown. We focused on host-related mechanisms to identify tumor-specific serum factors of mice bearing Ehrlich carcinoma, which have the potential to confer resistance towards tumor development. An experimental model was used, where we incubated isolated immune cells (peritoneal cells (PCs) and splenic lymphocytes (SLCs)) in vitro with blood serum or ascitic fluid from tumor-bearing mice. Mice inoculated with PCs or SLCs previously incubated for 7 h with ascitic fluid from tumor-bearing mice did not develop tumors at a frequency of 93.1+/-5.7% (inoculation of tumor cells after two weeks) and 100% (inoculation of tumor cells three months later). This indicates that mice developed resistance towards tumor development. By fractionation of ascitic fluid and (LC/MS-MS)-driven profiling of serum proteins, we identified serpin (alpha-1-antitrypsin), which was missing from the PC-incubated fraction, indicating that this protein was bound to PCs and, thereby, purged from the protein fraction. In parallel, cathepsin L1 appeared after incubation with PCs. Serpins play a central role in the regulation of a wide variety of (patho)-physiological processes, including coagulation, fibrinolysis, inflammation, development, tumor invasion and apoptosis. Furthermore, serpins may protect parasites against the immune systems of the host. Taken together, it can be hypothesized that serpin represents a tissue- and tumor-specific anti-proteinase.

In vitro effect of Knotolan, a new lignan from Abies sibirica, on the growth of hormone-dependent breast cancer cells.

Here we present antiestrogenic effects of Knotolan, a new dietary lignan from Abies sibirica raw material. Knotolan abolished growth-stimulating effects of 17ß-estradiol on hormone-dependent MCF-7 cells.