EDITORIAL
ORIGINAL RESEARCH
Background. According to current concepts regarding hepatic fibrosis, myofibroblast differentiation from stellate cells, regulated by transforming growth factor-β (TGF-β), is a key step in its pathogenesis. Hence, inhibition of TGF-β-dependent activation of hepatic stellate cells has been suggested as a promising strategy for preventing the disease development.
Aim. To explore whether the administration of fucoxanthin at a dose of 30 mg/kg is efficient in suppressing hepatic fibrosis.
Materials and Methods. The experiments were carried out on 30 outbred ICR/CD1 mice which have been divided into three groups: intact animals, animals with untreated hepatic fibrosis which has been induced by intraperitoneal injections of CCl4 (2 μl/g, 6 weeks, twice per week), and animals which received fucoxanthin per os (30 mg/kg daily for 5 weeks) after inducing hepatic fibrosis as described above. Histological examination was performed by Sirius Red staining using the METAVIR fibrosis and activity score. Immunohistochemical analysis was performed by quantitation of α-SMA-positive myofibroblasts, CD45-positive leukocytes, and TIMP-1-positive regions. Further, we quantified TGF-β in liver homogenate as well as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum by means of enzyme-linked immunosorbent assay. An assessment of liver function was conducted by measuring serum alanine aminotransferase, aspartate aminotransferase, and albumin levels.
Results. Fucoxanthin decreased the number of myofibroblasts and leukocytes, the volume of connective tissue and TIMP-1-positive regions, and the level of TGF-β in the liver homogenate, altogether indicative of ameliorated hepatic fibrosis. In accord, treatment with fucoxanthin reduced serum IL-1β, TNF-α, alanine aminotransferase and aspartate aminotransferase, and increased serum albumin.
Conclusion. Treatment with fucoxanthin at a dose of 30 mg/kg has an antifibrotic effect and diminishes liver fibrosis.
Aim. To study the possible synergistic action of steroid hormones and hormone-specific autoantibodies and anti-autoantibodies in conversion of ER+/PR+ tumors into ER-/PR- in breast cancer patients.
Materials and Methods. Concentrations of estradiol (E2) and progesterone (Pg) and the levels of hormone-specific idiotypic IgA antibodies (IgA1-E2 and IgA1-Pg) as well as anti-idiotypic IgG antibodies (IgG2-E2 and IgG2-Pg) were studied in the serum of 979 breast cancer patients (432 patients with stage 1 and 547 patients with stages 2-4) by means of enzyme-linked immunosorbent assay. E2 and Pg receptors phenotype (ER/ PR) was determined using immunohistochemistry.
Results. Simultaneous increase in IgA1-E2 and IgG2-E2 levels was associated with elevated E2 serum concentration (p = 0.007) in ER+/PR+ breast cancer patients. On the contrary, concurrent increase in IgA1-Pg и IgG2-Pg, was associated with lowered Pg concentration (p = 0.04). The frequency of ER+/PR+ tumors was low and ER-/PR- was high in patients with stages 2-4 breast cancer than in stage 1 in the following cases: 1) IgG2-E2 and IgA1-E2 levels were high regardless of serum E2 (p = 0.004); 2) IgG2-E2 levels were high and IgA1-E2 and E2 levels were low (p = 0.002); 3) IgG2-Pg and Pg levels were high regardless of IgA1-Pg levels (р < 0,001); 4) IgG2-E2 and IgG2-Pg levels were high regardless of E2, Pg, IgA1-E2 and IgA1-Pg levels (р < 0,001). In other combinations of hormones and hormone-specific antibodies and anti-antibodies, there have been no differences in the frequency of ER+/PR+ and ER-/PR- tumors between patients with ascending stages of breast cancer.
Conclusion. We for the first time found a synergistic action of hormone-specific idiotypic and anti-idiotypic autoantibodies on the concentration of steroid hormones in the serum of breast cancer patients, and the synergistic action of steroid hormones and hormone-specific idiotypic and anti-idiotypic autoantibodies on tumor steroid receptor conversion.
Aim. To compare placental morphology in patients with preterm birth and with full-term birth without gynecological infections.
Materials and Methods. We performed a retrospective, case-control study which included 150 women with vaginal delivery (50 women with preterm birth and 100 women with full-term birth). Placental tissues were studied by histological examination.
Results. Histological signs of placental immaturity were detected in all patients with preterm birth and were absent in those with full-term birth (p < 0.001). Placental insufficiency was diagnosed in 27 (54%) women with preterm birth and in 35 (35%) women with full-term birth (χ2 = 4.962, p = 0.026). Partial compensation of placental insufficiency was detected in 10 (20%) women with preterm birth and were not observed in patients with full-term birth. Signs of placental infection were registered in 32 (64%) women with preterm birth and 37 (37%) patients with full-term birth (χ2 = 9.783, p = 0.002). Chronic deciduitis was documented in 9 (18%) women with preterm birth and 7 (7%) women with full-term birth (χ2 = 4.233, p = 0.04), chronic histiocytic intervillositis was found in 16 (32%) women with preterm birth and 11 (11%) women with full-term birth (χ2=9.959, p=0.001), chorioamnionitis was diagnosed in 20 (40%) women with preterm birth and 25 (25%) women with full-term birth (χ2 = 3.571, p = 0.059), respectively. Purulent membranitis was detected only in 5 (10%) women with preterm birth.
Conclusion. Patients with preterm vaginal birth without gynecological infections are characterized by a higher prevalence of placental infections (64%) and placental insufficiency (54%) than women with full-term birth.
Aim. To determine the prevalence and features of menstrual dysfunction in premenopausal women of various ethnicities inhabitating Eastern Siberia.
Materials and Methods. We conducted a cross-sectional study which included women of reproductive age (18-44 years) living in the Irkutsk region and the Republic of Buryatia. Out of 1134 women, 715 (63.1%) were Caucasians, 312 (27.5%) were Asians (Mongoloid), and 107 (9.4%) were of mixed ethnicity. The data have been collected during the annual physical examination carried out between March 2016 to May 2021,
Results. The average age of menarche onset was 13.3 ± 1.4 years and did not differ significantly in Caucasians, Asians, and group of mixed ethnicities. The most frequent ages for menarche were 11 and 15 years among women of mixed ethnicity and Asians, respectively. Chronic abnormal uterine bleeding and dysmenorrhea was detected in 573/1134 (50.5%) and in 280/1134 (24.7%) of the examined women, respectively, without significant differences between the ethnicities. However, dysmenorrhea symptoms were more severe in Caucasians as compared to Asian women.
Conclusion. The most frequent variant of menstrual dysfunction is chronic abnormal uterine bleeding. There were no significant differences in the prevalence of irregular menstrual cycles, oligo/anovulation, chronic abnormal uterine bleeding, and dysmenorrhea in women of reproductive age belonging to different ethnicities, although clinical manifestations of dysmenorrhea were most pronounced in Caucasians.
Aim. Formation of polymorphic variants panel of the proteasome genes 20S, potentially significant for the study as balance modifier factors of p105/p50 NFKB1.
Materials and methods. Determination of genes that encode proteins of the multisubunit proteasome complex prospective for research purposes, was carried out on the basis of information retrieved from eLIBRARY and PubMed. The source of information for the formation of polymorphic variants panel of genes (SNP, single nucleotide polymorphism) was the Ensembl genomic browser, http://www.ensembl.org. The structure of genes is described by the NCBI (databases Gene, http:// www.ncbi.nlm.nih.gov/gene). The panel was filled with the minor allelic frequency in the population (MAF), the localization of SNP in the gene structure and the availability of data on the relationship with multifactorial diseases and other effects in mind. To calculate the genetic distances between populations, we used the methord of comparing the populations by frequencies of polymorphic marker alleles proposed by Ney, the obtained matrices are illustrated by the method of multidimensional scaling in space using Statistica v.8.0.
Results. Discussion of the algorithm and results of analytical screening of polymorphic variants of 14 genes (PSMA1-PSMA7, PSMB1–PSMB7) encoding proteasome subunits 20S. The characteristics of the SNP panel are given, compiled with the selection criteria taken into account. According to the data on the frequencies of polymorphic gene variants, the features of global and European population gene pools (283 SNP), as well as samples from Russian populations (20 SNP) are analyzed. Based on the results of the analysis of information on the associations of selected SNPs with various diseases, a panel (42 SNPs) of 20S proteasome genes was formed, potentially significant for the study as factors modifying the p105/p50 NFKB1 balance.
Conclusion. Annotation of the formed panel of SNP genes of the 20S proteasome with MAF>0.1 indicates the potential role of polymorphism in the pathogenesis of diseases of various profiles. This may be of research interest to the formed panel in context of implementation of traditional approaches – the search for candidate genes based on the analysis of associations with diseases, as well as the analysis of the influence of SNP on the level of genetic expression, synthesis of gene products, NFKB1 processing and p105/p50 balance in silico and on model objects.
Aim. To study the airborne transmission of acute respiratory viral infections (ARVIs) in medical care workers of dental clinics.
Materials and Methods. We developed a simulation model in which the bacteriophage E. coli, which is a part of the drug "Intesti-bacteriophage", was used as a model of the virus. The host bacterium was Escherichia coli strain M-17, which is part of the Kolibakterin drug. The phage titer according to Appelman was 10-5 plaque-forming units per mL. The experiment was conducted in outpatient care dental office with the participation of medical care workers and implied the contamination of the dental dummy oral cavity by the bacteriophage (A-Dec Simulator REF: 4820) during the treatment of tooth decay by means of aerosol-generating technologies and further detection of the bacteriophage in the environment. Bacteriophage spread was evaluated in 5 series of experiments by collecting the samples from dental office air (n = 50), surfaces of equipment (n = 90), and personal protective equipment of a dentist (n = 80).
Results. We found an intensive contamination by bacteriophages during the treatment of tooth decay with the use of aerosol-generating technologies. Phage was isolated in all air samples in the treatment area (100.00% [95% CI 47.82-134.48]) and in 20% of samples at a distance of 160 cm (near the exit). Bacteriophages spread by air currents contaminated the personal protective equipment: protective glasses, gloves, and sleeves of a robe in 100.00% [95% CI 47.82-134.48]) of samples. We have also found a frequent contamination of the inner surface of glasses (40.00% [95% CI 5.27-85.34]) and a medical mask (80.00% [95% CI 28.36-99.49]).
Conclusion. We developed a model to study the airborne transmission of ARVI pathogens spread during dental care. Intensive phage contamination of the dental office air and personal protective equipment has been established. A detailed study of the airborne transmission of ARVIs is necessary to improve their prevention in dental workers.
Aim. To assessment the prevalence of cancer risk factors in various population groups of the Omsk region.
Materials and Methods. The descriptive, cross-sectional epidemiological study included residents of the Omsk region (n = 542) aged 18 to 83 years. To obtain the data, we performed a survey which included questionnaires on the daily patterns and frequency of food consumption, eating habits, and health status. In addition, we assessed the prevalence of smoking, alcohol consumption, physical activity, family history of cancer, overweight.
Results. At least one of the studied risk factors was present in 80.1 ± 1.7% of the adult population, including 84.9% of men and 76.3% of women (p = 0.030). The most common factors were: excessive consumption (> 500 g/week) of red and processed meat (55.8 ± 2.1%), overweight (53.6 ± 2.1%), excessive consumption of dietary salt (44.2 ± 2.1%), frequent alcohol consumption (39.3 ± 2.1%), and low physical activity (29.8 ± 2.1%). The smoking was more prevalent in the male population (37.0 ± 3.13%). Although overall alcohol consumption was below the Russian average, excessive alcohol consumption was still found in 21.9% of men and 12.8% of women. The combination of smoking and excessive consumption of alcohol was also more frequent in male population (26.8 ± 2.1%). The proportion of people with consumption of fresh vegetables and fruits < 500 g/day (including potatoes) was 42.6 ± 2.12%. The content of dietary fiber in the diet in an amount < 20 g/day was noted in 57.8 ± 2.1% of the study participants. In men, the average daily salt intake was significantly higher compared to women (6.24 g and 5.20 g, respectively; p = 0.001).
Conclusion. The prevalence of cancer risk factors among the residents of the Omsk region was assessed as high and generally does not tend to decrease.
Aim. To evaluate the incidence and causes of peptic ulcers of the gastrojejunal anastomosis to develop the corresponding preventive measures.
Materials and Methods. We retrospectively analysed the case histories of the patients with peptic ulcer who have been admitted to our surgical unit during 1981-1996 and 2007-2021. A total of 62 patients with peptic ulcers of the anastomosis who underwent Billroth II resection were examined radiographically, endoscopically, and intraoperatively, including proteolysis and acidity measurements.
Results. While the number of gastric operations has been reduced by 86%, the number of treated peptic anastomotic ulcers decreased by only 20%. The main cause of peptic ulcers was the high acidity and proteolytic activity of the gastric stump. In 22 out of 28 fully examined patients, duodenal ulcer was treated by hemiresection. The incidence of peptic ulcers of gastrojejunal anastomosis in Kemerovo in 2021 was 0.9 per 100,000 population, with 3.7 Billroth II surgeries per 100,000 population. A resection without vagotomy and insufficient acid reduction are the main causes of peptic ulcers of the gastrointestinal anastomosis, especially duodenal ulcers.
Conclusion. A significant decrease in the number of distal resections of the stomach according to Billroth II over the past 25 years is not accompanied by a similar decline in the number of hospitalized patients with peptic ulcers of the gastrojejunal anastomosis.
Aim. To identify predictors of ischemic and hemorrhagic events in patients with myocardial infarction (MI) after 18 months of follow-up.
Material and Methods. The single-center prospective study included 478 patients with MI. The exclusion criteria were as follows: age < 18 years; MI as a complication of myocardial revascularization; atrial fibrillation; intake of anticoagulants after MI. During inpatient treatment, the risk of ischemic and hemorrhagic events was calculated according to the PRECISE-DAPT score, GRACE hospital discharge risk score, CRUSADE bleeding score. After 18 months, we evaluated the rate of ischemic (cardiovascular death, unstable angina, life-threatening arrhythmia, non-fatal MI and stroke, acute decompensated heart failure, elective repeated and/ or emergency revascularization) and haemorrhagic events and the amount of corresponding therapy.
Results. At 18 months post-MI, patients were at high risk of developing both ischemic events (cardiovascular death: 32.0%; recurrent MI: 16.3%; repeated myocardial revascularization: 18.5%; unstable angina: 13.8%; stroke: 3.6%) and hemorrhagic events (bleeding rate of 39.7% according to the TIMI score), most of which occurred during the first 12 months post-MI. Double antiplatelet therapy (DAPT) was prescribed to 86.5% patients upon discharge (including a triple antithrombotic therapy in 8.6% patients). Patient adherence to treatment was 66.7% and 60.6% at 6 and 12 months of follow-up, respectively. After 18 months, DAPT was prescribed exclusively to patients suffered from recurrent ischemic events or those who underwent repeated myocardial revascularization (17.4% patients in total). The main reason to cancel DAPT was bleeding, although it was minor in most cases. Predictors of ischemic events (fatal and non-fatal) at 18 months of follow-up were PRECISE- DAPT score (odds ratio (OR) = 1.108, 95% confidence interval (CI) = 1.054-1.164, р < 0.001), GRACE score (OR = 1.032, 95% CI = 1.016-1.048, р < 0.001), left ventricular ejection fraction (LVEF) < 40% (OR = 4.256, 95% CI = 1.510-12.001, р = 0.006). Predictors of hemorrhagic events at 18-month follow-up were PRECISE-DAPT score (OR = 1.025, 95% CI = 1.009-1.041, р = 0.002), peripheral artery disease (PAD) (OR = 2.459, 95% CI = 1.365-4.428, р = 0.003), intake of sulfonylurea for diabetes mellitus (OR = 2.523, 95% CI = 1.266-5.028; р = 0.009), unsuccessful percutaneous coronary intervention (PCI) or conservative treatment of MI (OR = 3.792, 95% CI = 1.799-7.996, р < 0.001).
Conclusion. Predictors of ischemic events (fatal and non-fatal) in the long-term period after MI include PRECISE-DAPT and GRACE scores, and LVEF below 40%. Predictors of hemorrhagic events at 18-month follow-up were PRECISE- DAPT scores, PAD, taking sulfonylurea for diabetes mellitus, unsuccessful PCI or conservative treatment of MI.
REVIEW ARTICLES
Here we provide the recent information on the molecular profile of the endometrium and highlight the pathogenesis of infertility occurring during endometriosis. Because of individual features of each woman’s organism, there are no versatile diagnostic criteria for determining endometrial receptivity which plays one of the leading roles in implantation disorders. Although a lot of studies on the gene expression in endometriosis have been published to date, intricate gene-gene and gene-environment interactions frequently balance inherited or acquired alterations of gene expression in the endometrium. Hence, investigation of entire cell signaling pathways is preferrable over the general expression of gene expression within the endometrium. As eutopic and ectopic endometrium have largely similar histological appearance, the development of a single diagnostic test remains an unmet clinical need. Therefore, it is urgent to search for novel, evidence-based criteria for timely prediction and early diagnosis of endometriosis-associated infertility using minimally invasive examination methods.
Aim. To perform a systematic review of common risk factors and prognostic markers of gestational diabetes mellitus (GDM) and hypothyroidism (HT), as well as maternal and perinatal complications in these diseases. For achieving this task, we screened and analysed the relevant data from the publications in a PubMed database over the past 6 years.
Key Points. A common risk factor for both diseases is obesity, which is characterized by pregestational insulin resistance, as well as the combination of by low-grade chronic inflammation and metabolic dysfunction termed as meta-inflammation. Antibodies to the thyroid-stimulating hormone receptor (TSHR) are associated with the reduced the risk of GDM. Studies on pathogenesis of pre-eclampsia in patients with GDM and HT have shown unequivocal results, although most of them suggest both HT and GDM as risk factors for the development of this pregnancy complication. Elevated levels of thyroid-stimulating hormone are associated with reduced antioxidant capacity and long-term endothelial activation. The heterogeneity of the anemia in GDM requires a rigorous differential diagnosis.
Conclusion. GDM and HT are the most common endocrine diseases during pregnancy which significantly increase the risk of maternal and perinatal complications. Common risk factors, interrelationship, and ambiguous data on GDM and HT development mechanisms indicate the need for screening and detailed monitoring of patients with thyroid dysfunction for early detection and correction of hyperglycemia.
Respiratory homeostasis is fine-tuned system largely dependent on the clearance of inhaled substances from both upper and lower airways. The least studied is alveolar clearance, which, however, is crucial for the proper lung function and requires a detailed examination in order to improve the accuracy of diagnosis and treatment of lung diseases. Here, I analysed relevant literature from publicly available databases (Index Medicus, PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Google Patents) to compare various methods for determining alveolar clearance, their advantages and shortcomings, their applicability in routine clinical practice and prospects for their use. The most accessible, informative, and inexpensive method to assess the alveolar clearance is bronchoalveolar lavage and the study of bronchoalveolar lavage fluid. Confocal laser endomicroscopy, a new and powerful imaging modality, has not been widely implemented hitherto. A non-invasive inhalation of a radioaerosol tracer for studying alveolar clearance in vivo seems to be promising but still requires adaptation for the broad use.
CASE REPORTS
Here we describe a rare case of an abnormal karyotype with a supernumerary derivative chromosome der(22)t(11;22), associated with Emanuel syndrome, in a boy aged 1 year. Familial cytogenetic analysis revealed the maternal origin of the anomaly from reciprocal translocation t(11;22) (q23;q11.2). At the time of the examination, the child had numerous anomalies of development, facial dysmorphia, and a small size of the external genitalia. In addition, there was a pronounced delay in psychomotor development because of the brain damage. We made an attempt to perform a comprehensive analysis of the risks to the patient's health by generalizing the cases of Emanuel syndrome described in the literature.
ISSN 2542-0941 (Online)