The Effectiveness of Local Application of Melatonin in the Original Dermal Film in Experimental Thermal Trauma

Background: The development and pathogenetic substantiation of the new agents used for local therapy of thermal trauma (TT) is an urgent problem in medicine. Melatonin (MT) is an endogenous factor of homeostasis regulation with pleiotropic potential. The aim of our study was to assess the morphology, expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), indicators of repair, oxidative destruction of lipids in the skin lesion focus in the dynamics of experimental TT under the conditions of using the original dermal film (DF) with MT. Methods and Results: The experiment was performed on 104 male Wistar rats weighing 200-240 g. For modeling TT II degree according to ICD-10 a relative area of 3.5% of the body surface, an interscapular region isolated from the surrounding tissues, was immersed in distilled water at 98-99 °C for 12 sec. DF based on sodium carboxymethylcellulose with an area of 12 cm2 with MT at a concentration of 5 mg/g was applied daily for five days. The wound area and epithelialization rate were calculated. The content of MMP-9 and VEGF in the burn wound was assessed by an immunohistochemical method. In the homogenate of the burn wound, the content of LPO products was assessed. Morphological and biochemical studies were performed on Days 5, 10 and 20 after TT induction. With experimental TT from Day 5 to Day 20, the absolute area of the burn wound decreases by 35%, the rate of epithelialization increases, the number of neutrophils in the focus of thermal damage decreases, while the representation of lymphocytes, histiocytes, and fibroblasts increases; the expression of MMP-9 and VEGF increases; predominantly secondary and final LPO products in the heptane phase accumulate, the final products of LPO in the isopropanol phase of the lipid extract. The use of MT in the composition of DF daily for 5 days with experimental TT leads to a decrease in the area of the wound defect (by 46% of the original area on Day 20), an increase in the rate of its epithelialization, an increase in the content of lymphocytes and fibroblasts in the burn wound on Days 5, 10 and 20 of TT, a decrease in the representation of neutrophils and macrophages on Days 5 and 10, as well as an increase in VEGF expression on Days 5 and 10, MMP-9 - on Day 5 and a decrease in MMP-9 expression on Days 10 and 20 of TT. In addition, the use of MT in the composition of DF leads to a decrease in the content of predominantly secondary and end products of LPO in the heptane and isopropanol phases of the burn wound on Days 10 and 20 of TT. Correlation analysis revealed that a decrease in the burn surface area under a local application of MT occurs with an increase in the content of VEGF in the wound area and a decrease in the content of MMP-9 and secondary and final LPO products in the heptane phase and the isopropanol phase. On Day 20, there were direct moderate correlations between the absolute burn surface area, on one hand, and secondary and final LPO products, on the other, in the heptane phase (R=0.51, R=0,68; P<0.05) and the isopropanol phase (R=0.44, R=0.46; P<0.05), respectively. Conclusion: The results obtained expand the existing understanding of the role of changes in the expression of MMP-9 and VEGF in the pathogenesis of TT. We believe that the repair-stimulating effect of MT in the DF, which we established during TT at the preclinical stage, is associated with the LPO-limiting effect of MT and a change in the expression of MMP-9 and VEGF in the burn wound and is a prerequisite for further study of the mechanism of action and the effectiveness of MT application in clinical conditions in TT.

MTHFR and MDR1 Gene Polymorphisms in Yakut Patients with Non-Syndromic Orofacial Clefts

The aim of our study was to investigate the relationship between the MDR1 and MTHFR gene polymorphisms and non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Yakut population in the Republic of Sakha (Yakutia). Methods and Results: The sample of examined persons consisted of 60 children with NSCL/P. The NSCL/P group was divided into the CLP (cleft lip with cleft palate) subgroup (n=31), CLO (cleft lip only) subgroup (n=14), and CPO (cleft palate only) subgroup (n=15). The comparison group (control) included 174 healthy volunteers who did not have relatives with OFCs. The study of the MDR1 rs1045642 SNP and the MTHFR rs1801133 SNP was performed by PCR and RFLP analysis. Analysis of the frequency distribution of alleles and genotypes depending on the severity of clefts showed that the carriage of the TT homozygous genotype of the MDR1 rs1045642 SNP was associated with significant risk for the development of NSCL/P (OR=2.52, 95% CI: 1.19-5.32, P=0.02). Analysis of the recessive model (TT vs CC + TC) also found a significant risk of NSCL/P with the TT genotype carriage (OR=2.20, 95% CI: 1.06-4.57, P=0.04). Analysis of the over-dominant model (TC vs TT + CC) showed that the heterozygous TC genotype had a protective effect (OR=0.41; 95% CI: 0.22-0.77, P=0.01) on the development of NSCL/P. Subgroup analysis according to NSCL/P subtypes (CLO, CPO and CLP) showed that the MDR1 rs1045642 SNP was significantly associated with a high risk of CPO in three genetic models: heterozygous [(TT vs TC): OR=5.03; 95% CI: 1.55-16.32; P=0.01], recessive [(TT vs CC + TC): OR=3.96; 95% CI: 1.32-11.95; P=0.02], and over-dominant [(TC vs TT + CC): OR=0.23; 95% CI: 0.08-0.66; P=0.01]. Conclusion: A study of two SNPs in the MDR1and MTHFR genes revealed a statistically significant increased risk for NSCL/P in carriers of the TT genotype of the MDR1 rs1045642 SNP.

Modern Clinical and Epidemiological Features and New Technological Possibilities in the Treatment of Bleeding Gastroduodenal Ulcers

The aim of this research was to study the current clinical and epidemiological features of ulcerative gastroduodenal bleeding (GDB) and to evaluate the outcomes of using new technological approaches in patients with bleeding from acute (symptomatic) and chronic (peptic ulcer disease) gastroduodenal ulcers (GDUs). Methods and Results: The present study involved 221 patients with bleeding GDUs. Depending on the source of bleeding, all patients were divided into 2 groups. Group 1 included 143 patients with acute symptomatic GDUs; Group 2 consisted of 78 patients with peptic ulcer disease complicated by bleeding. In the complex treatment of patients of all the studied groups, an individual approach was used that included the innovative technologies of endoscopic cytoprotective treatment of GDB, based on the combined use of traditional means of EH in combination with the use of endoscopic pneumoinsufflation of biologically active drainage sorbent of a new generation Aseptisorb-D and powdered hemostatic Zhelplastan. Our analysis showed that acute symptomatic GDUs prevailed in the structure of GDB – 143(64.7%) patients; PUD complicated by bleeding was diagnosed in 78(35.3%) cases. The use of new technological approaches, including cytoprotective treatment of bleeding defects with biologically active draining sorbents of a new generation in combination with local hemostatics in the complex therapy of patients with ulcerative GDB, has significantly improved the results of treatment, which is confirmed by high rates of final hemostasis (95.0%), indicators of the effectiveness of primary EH in type FIA-IB (93.1%) and prevention of recurrence of FIIA-IIB bleeding (92.5%), with a low frequency of repeated bleeding (4.07%), emergency surgeries (2.7%), and mortality (3.2%). Conclusion: Currently, in the structure of ulcerative GDB, acute symptomatic GDUs are the most common – 64.7%, and the share of PUD complicated by bleeding accounts for 35.3% of cases only. PUD and GDUs complicated by bleeding have certain clinical and epidemiological features, which must be taken into account when treating these patients. Symptomatic GDUs are more difficult to treat, which shows the need to develop new complex technologies for their treatment.

Effect of the p38 MAPK Inhibitor on the Expression of Metalloproteinases and Their Inhibitors during the Formation of Abdominal Adhesions

Background: The aim of this study was to assess the effect of blockade of the p38 mitogen-activated protein kinase (MAPK) on the expression of genes encoding metalloproteinases (MMPs) during the formation of adhesions in the abdominal cavity. Methods and Results: The experiments were carried out on male Wistar rats (n=75). The studies were carried out in two groups: Group 1 (control, n=35) – modelling the adhesive process; Group 2 (experimental, n=35) – modelling the adhesive process with intraperitoneal administration of Seroguard®—a prolonged form of the p38 MAPK inhibitor. The expression of the MMP1a, MMP2, MMP7, MMP9, and TIMP genes was assessed using real-time PCR. In the control group, overexpression of the MMP1a and MMP7 genes began from 6 hours after modeling the adhesive process, MMP9 – from Day 1, MMP2 – from Day 7 and persisted until the end of observation. With local blockade of p38 MAPK, the level of overexpression of genes encoding MMPs in the early stages was higher than in the control group (MMP1a – by Day 1; MMP7 – by 6 hours and Day 1, MMP9 – by 12 hours). From Day 3 to Day 14, the MMP1a and MMP7 expression in the experimental group was significantly lower than in the control group. Conclusion: The performed study demonstrated the involvement of different types of MMPs—collagenases (MMP1a), gelatinases (MMP2 and 9), matrilysins (MMP7)—in the rearrangement of the extracellular matrix during the process of adhesion formation in the abdominal cavity.

The Role of Physical Aerobic Activity in Controlling Exercise-Induced Bronchoconstriction in Children and Adolescents with Asthma

Asthma, one of the major widespread chronic disorders among children and adolescents, has become more prevalent recently. The common manifestations of this disorder are caused by inflammatory airways that lead to airway restriction and lung hypersensitivity causing dry coughing, wheezing, and shortness of breath, all of which are combined with sleep disturbance, impaired physical activity, and reduced quality of life. The main goal of this brief review was to identify the associated variables that affect the management of asthma disease in children and young adolescents and to identify the role of physical aerobic exercise in the treatment of asthmatic children. The current review was based on prior research published in English databases such as Google Scholar, PubMed, and Embase in scientific articles published between January 2010 and October 2021 with the keywords "asthma," "children," "adolescents," "breathing episodes," "physical activity," and "physical exercise." Regular physical aerobic exercise training with moderate intensity has been shown to improve pulmonary functions, life quality, psychological conditions, and reduce asthma symptoms and EIB in children and adolescents with bronchial asthma.

Microbiological Study of Vaginal Microbiota and Endometrium in Women with Chronic Endometritis

The research objective was to study the spectrum of the vagina and endometrium microorganisms in women with chronic endometritis (CE) in order to take adequate therapeutic measures. Methods and Results: We did a cross-sectional study in 47 women (average age of 35.38±5.19 years) with histologically confirmed CE. The vaginal microbiota and endometrial biopsies were assessed using microbiological research methods in accordance with the medical technology "Integral assessment of the state of the vaginal microbiota." To identify the share of different types of microorganisms in the structure of the biocenosis, the coefficient of constancy of the species (C) was used. Only 19% of patients had a titer of Lactobacillus spp. within the age norm, while the deficit was observed in 80% of women. Among the representatives of Enterobacteriaecae, Escherichia coli and Klebsiella aerogenes were sown, which are considered to be random species (C=11% and C=2.1%, respectively). The average titer for E. coli was 3.6±1.3 lg CFU/swab and for K. aerogenes - 2.14 lg CFU/swab. An atypical variant of E. coli with hemolytic properties was found in only one sample. All isolates of the genus Staphylococcus were also random species (C did not exceed 25%). Coagulase-negative staphylococci (CoNS) were detected in 7 patients (C=15%), while the average titer was 2.1±0.4 lg CFU/swab. S. aureus was isolated from only one patient at a titer of 5 lg CFU/swab. Corynebacterium spp. were isolated in 11% of cases (C = 11% - random species), in a titer of 3.2±0.8 lg CFU/swab. Enterococcus spp. also belonged to random species (C=23.4%). At the same time, E. faecalis was inoculated in 19% of cases and E. faecium was sown in 4.3%, the average titer of which was 3.1±0.9 and 5 lg CFU/swab. Streptococcus spp. were recorded in only one case at a concentration of 5 lg CFU/swab. Fungi of the Candida were isolated as a random species in 8.5% of cases. The growth of microorganisms in endometrial samples was obtained only in 3 examined women with CE (6.4% of cases). The endometrial microbiota were represented only by random species, for which the C index ranged from 2.1% to 4.3%. Conclusion: The microbiological study of the microbiota of vaginal discharge showed the presence of dysbiotic disorders with a significant deficiency of lactobacilli (80%) without the dominance of representatives of the Lactobacillus spp. In the structure of opportunistic microflora, Escherichia coli, coagulase-negative staphylococcus, Enterococcus spp., and E. faecalis prevailed as random species. Representatives of the microbiota in endometrial biopsies were identified only in 6.4% of cases, and are represented by random species.

Production, Properties and Swelling of Composite Agar-Pectic Gel Particles in an Artificial Gastroenteric Environment

The purpose of the present work was to obtain and study the properties of composite calcium-agar-pectic gel particles (CaAPGPs) obtained from aqueous solutions of agar (AA) and apple pectin (AP), from aqueous solutions of agar (AA) and pectin heracleuman (HS) in the presence of Ca2+ ions (0.34 M). The swelling of the obtained composite CaAPGPs in an artificial gastroenteric environment was also investigated. Methods and Results: We used commercial AP AU701 (AP, Herbstreith & Fox KG, Germany), HS isolated from the aerial part of the Sosnovskyi hogweed Heracleum sosnowskyi Manden, and food agar (AA). Spherical composite CaAPGPs were obtained from low-methyl esterified AP with a molecular weight of 406 kDa, pectin HS with a molecular weight >300 kDa, and food agar (AA) in the presence of Ca2+ ions (0.34 M) as a cross-linking agent by the method of ionotropic gelation. It was found that dry CaAPGPs based on AP (Ca-AA-AP) have a diameter of 1.16±0.14-1.23±0.05 mm, which was greater than the diameter of dry CaAPGPs based on HS (Ca-AA-HS) (0.95±0.12-1.16±0.05 mm). The density of dry CaAPGPs based on AP (Ca-AA-AP) with an increase in the concentration of AP in their composition from 1% to 2% increased by 1.7 times – from 0.37±0.07 mg/mm3 to 0.63±0.05 mg/mm3. Dry composite CaAPGPs based on HS (Ca-AA-HS) were denser. With an increase in the HS concentration in their composition from 1% to 2%, the degree of particle density increases by 2.2 – from 0.45±0.03 mg/mm3 to 0.97±0.19 mg/mm3. The swelling and degradation of the obtained dry composite CaAPGPs in an artificial gastroenteric environment were studied. It was found that CaAPGPs formed from 1% AP and 2% AA degraded almost immediately in SIF. Whereas, CaAPGPs formed from 2% AP and 1% or 2% AA completely degraded in SCF after 1 hour of incubation in it. CaAPGPs formed from 1% HS and 2% AA, and particles obtained from 2% HS and 1% AA, remained stable in SIF, and then completely degraded immediately upon entering in SCF. CaAPGPs, consisting of 2% HS and 2% AA, dissolve in SCF after 1 hour of incubation in it.

Complications of the Early Neonatal Period in Children from Mothers with Gestational Diabetes Mellitus

Background: Changes in the course of gestational diabetes mellitus (GDM) at the present stage determine the emergence of a certain spectrum of completely new problems associated with the health status of newborns from mothers with GDM. The aim of the study was to investigate early neonatal complications in newborns from mothers with GDM. Methods and Results: The study included 404 pregnant women (gestational age of 37.0–41.0 weeks) with GDM. All patients with GDM were divided into 2 groups. Group 1 included 188 patients receiving insulin therapy; Group 2 included 216 patients receiving a well-balanced diet. The control group (Group 3) consisted of 68 pregnant women without disorders of carbohydrate metabolism. In Group 1, macrosomia occurred in 44(23.4%) newborns, in Group 2 - in 48(22.0%) newborns; in newborns from mothers of the control group, the frequency of macrosomia was only in 7.35% of newborns (P=0.01). Morpho-functional immaturity of newborns had the highest frequency of occurrence, despite the fact that all children were born on time; 80(42.6%) newborns from mothers of Group 1 and 77(35.6%) newborns from mothers of Group 2 had signs of morpho-functional immaturity. Conclusion: Diabetic fetopathy in newborns from mothers with GDM is manifested by morpho-functional immaturity of organs and systems developing in unfavorable hyperglycemic conditions.

Socio-Demographic Factors and Epidemiological Characteristics of HIV-Positive Pregnant Women with High Risk of Vertical Transmission of the Immunodeficiency Virus

The purpose of this study was to determine the features of the course of pregnancy, delivery, and the postpartum period in HIV-positive women with a high risk of HIV vertical transmission. Methods and Results: A retrospective, longitudinal cohort study of mother-child pairs for the period from 2017 to 2019 was conducted in the Irkutsk City Perinatal Center (level III). The clinical observation group included HIV-positive women (n=213) and their newborn children with a high risk of perinatal immunodeficiency virus transmission (n=214). The findings of the conducted study demonstrated that most HIV-seropositive women with a high risk of HIV vertical transmission had an aggravated social history, a high prevalence of pelvic inflammatory diseases, and a high incidence of opportunistic and AIDS-defining conditions. Evaluation of PMTCT preventive complex showed that the target parameters in women with a high risk of HIV transmission were not reached: the first stage was performed for 49.3% of pregnant women with good ART adherence, the second stage – for 97.1% of obstetric patients, the third stage – in 100% of HIV perinatally exposed children. HIV RNA was detected in 3.7% of children, which evidences their antenatal infection. Conclusion: Development of efficient communication with HIV-positive women aimed at preservation of their health and decrease of logistic barriers to access to medical care.

Interaction of Long-Chain Alcohol with Dry Yeast, Cholesterol, and Sea Firefly Luciferase

Background: A hand sanitizer containing alcohol, usually ethanol or isopropanol, is typically used for disinfection, but given that cholesterol is one of the main components of virus envelopes, long-chain alcohol may be more effective. To better understand the potential disinfection activity of long-chain alcohols, we studied their interactions with dry yeast, cholesterol, and sea firefly luciferase. Methods and Results: We measured, at 30oC and 39oC, the minimum inhibition concentration (MIC) of dry yeast fermentation and the stability of cholesterol and sea firefly luciferase with alcohols, diols, cetyltrimethylammonium chloride, and stearyltrimethylammonium chloride. The MIC decreased with the chain length at C≤12 for dry yeast and cholesterol with alcohol at 30oC. At C13 and higher, the cut-off region was observed. At 39oC, the cut-off region shifted to C15 and higher. The reduction of MIC was measured with the diol or sea firefly luciferase at C≤14. Conclusion: The presence of the cut-off region is suggested to be related to whether the alcohol is in the liquid state. For the liquid alcohol, the longer the chain length, the lower the MIC. This suggests a potential disinfection activity of long-chain alcohol.