Background. Heart transplantation is currently the treatment of choice for patients in terminal stages of chronic heart failure. The critical shortage of donor organs and the growing need for heart transplantation necessitate the expansion of donor selection criteria, including the estimated ischemia time of the donor heart. Despite numerous studies, the issue remains regarding the safe cold ischemia time; no definite limit to the acceptable preservation time is known and no relevant pathomorphological data are available on the state of the donor heart myocardium at different time parameters. Objective. To comparatively assess the features of cardiomyocyte pathomorphology and expression of protein markers (actin and desmin) in the myocardium of a donor heart prior to the main stage of orthotopic heart transplantation. Methods. The work adopted the design of an observational clinical study, which was prospective in nature. The study used intraoperative myocardial biopsy specimens of the left atrial appendage from donors aged up to 60 years, following cold ischemia of the transplant in Bretschneider solution (Dr. Franz Köhler Chemie GmbH, Germany) lasting up to 240 minutes (Group 1, n = 10) and over 240 minutes (Group 2, n = 7). The nature of pathomorphological myocardial transformation in the left atrial appendage of the donor heart was determined at different cold ischemia times. Histological myocardial sections were stained with hematoxylin and eosin according to standard procedures. After that, they were further studied using light and polarization microscopy; the immunohistochemical method was used to analyze the expression of actin and desmin. Morphometry was performed using the ImageJ 1.48v software (USA). In the analysis of actin and desmin amount, the area of DAB(3,3′-diaminobenzidine)-positive products of the immunohistochemical reaction was estimated as a percentage of the image area. The volume density of immunohistochemically detectable actin and desmin was determined using 20 images at a magnification of 40×10. In order to study the intensity of the immune reaction, a semiquantitative method was used, which involved counting the number of cells in 25 randomly selected fields of view. The types of myocardial contracture damage were assessed via polarization microscopy. Results. Patients included in the first and second groups were comparable in terms of mean age and anthropometric indices. The mean age of patients amounted to 50 [44;59] years in Group 1 and 50 [49;50] years in Group 2, р = 0.193. The body mass index was 25 [22;27] in Group1 and 25 [21;31] in Group 2, р = 0.288. Both groups showed male predominance: 8 (80%) in Group 1 and 6 (85.7%) in Group 2, р = 0.256. The comprehensive morphological assessment of ischemic myocardial damage at different cold ischemia times revealed the uniformity and reversibility of changes in cellular structures (in both groups) that take the form of I–II class contractures, lysis changes in individual cardiomyocytes (only in Group 2), preserved immunohistochemical reactions to actin and desmin in both groups at their average intensity and the complete absence of areas showing no reaction to desmin, which gives an idea about the degree of preservation of their macromolecular structure. Conclusion. The obtained study results showed that due to having a balanced elemental composition that determines the metabolic protection of cells and their ionic balance, the Bretschneider solution effectively protects the donor heart during its transportation, with the myocardial cold ischemia lasting up to 240 min and more.

Background. Periodontitis is a progressive lesion of periodontal tissues and one of the most important causes of tooth loss. According to recent publications, periodontitis affects from 11% to 50% of the world’s adult population. Therefore, the problem of developing effective methods for treating and preventing this disease remains relevant. Metabolic disorders in the periodontium are known to contribute to the development of periodontitis. A pronounced change in hemodynamics and microcirculation leads to trophic disturbance of periodontal tissues, thus triggering the development of pronounced hypoxia in these tissues. Thus, prevention and elimination of hypoxia is one of the most important stages of pathogenetic treatment. Objective. To experimentally evaluate the efficacy of injectable carboxytherapy in the treatment of periodontal diseases using an in vivo model of periodontitis in rats. Methods. A preclinical experimental study was conducted on 30 sexually mature Wistar rats. The animals were randomly divided into 4 groups, including I–III experimental groups (n = 27) and a control group (n = 3). In all experimental groups, periodontitis was modelled. In group I (n = 9), no treatment was performed. In group II (n = 9), carboxytherapy with a carbon dioxide flow rate of 5 ml/min was conducted. In group III (n = 9), carboxytherapy with a flow rate of 10 ml/ min was conducted. The experimental animals were injected with carbon dioxide once, twice, or three times 7 days after surgical intervention at weekly intervals. The efficacy of injected carboxytherapy in rat periodontium with respect to the control was evaluated by histologic analysis. The norm criteria were the lamellar structure of compact alveolar bone, the presence of periodontal ligament between the alveolar bone and the tooth, represented by oriented collagen fibers with orderly arranged fibroblasts between them (final signs). The intermediate outcome was considered based on the launch of neovascularization and neocollagenogenesis processes. The criterion of neovascularization and neocollagenogenesis activation was considered to be an increase in the number of young collagen fibers, an increase in fibroblast-like cells of outgrowth form with a high expression of procollagen in the connective tissue matrix (intermediate signs). Integral indices on intermediate signs and on final signs were brought to normalized indices as a fraction of the maximum possible sum of points in the group. The dynamics of the normalized indicator for intermediate and final signs was considered. The results were processed using IBM SPSS Statistics version 26 (IBM Inc., USA). Results. The histological study of the mandible of rats from group I demonstrated that the destruction of the periodontal ligament in the absence of treatment leads to the widening of the periodontal gap, accompanied by inflammatory processes and thinning of collagen fibers due to the growth of edema, the appearance of resorption lacunae and, further, to the resorption of alveolar bone. At the same time, groups II and III showed a gradual decrease in the inflammatory reaction, formation of young collagen fibers, and, as a consequence, restoration of the periodontal space. In these groups, the histologic pattern corresponded to the norm in the case of three times carboxytherapy injection with a flow rate of 5 ml/min and already in the case of two times injection with a flow rate of 10 ml/min. Conclusion. The use of injectable carboxytherapy to treat periodontal ligament lesions not only restores its microarchitectonics, but also prevents further resorption of alveolar bone. This may have a positive effect in the treatment of periodontal disease.

Background. Worldwide, more than 67 million people suffer from glaucoma. In Russia, this number exceeds 1.08 million people. Annually, the number of primary cases increases by 3–4%. The increasing prevalence of glaucoma intensifies the search for neuroprotectants that can reduce the loss of retinal ganglion cells, thereby impeding the progression of the disease. Objective. To study of the pharmacological activity of mGLUR4 agonist, ZC64-0001 substance, on a model of primary open-angle glaucoma. Methods. The conducted preclinical study involved 60 sexually mature male Wistar rats, weighing 180–220 g. The observation period was 73 days. The animals were divided into 6 groups with 10 animals in each. Group 1 included intact animals (without any manipulations); Group 2 included negative control animals with the water injected in the anterior chamber of the eye; in Group 3–6, primary open-angle glaucoma was modelled by injecting 1% hyaluronic acid solution into the anterior chamber of the eye once every 7 days from day 1 to day 62 of the study. Animals in Group 4 were treated intragastrically with H-[(4-chlorophenyl)methyl]-1,6-dihydro-4-methoxy-1-(2-methylphenyl)-6-oxo-3-pyridazinecarboxamide under the laboratory code of ZC64-0001 at a dose of 10 mg/kg. Animals in Group 5 received Mexidol as a comparison drug intramuscularly at a dose of 25.7 mg/kg. Animals in Group 6 were treated with a Timolol instillation at a dose of 0.009 ml/kg. The studied compounds were administered from day 63 of the study once a day for 10 days. The evaluated indicators included the level of microcirculation in the retina, the amplitude of a-wave and b-wave of the electroretinogram, and the number of retinal ganglionic layer nuclei in the setting of the conducted treatment. Statistical processing of the data was performed using the Statistica 10.0 software (StatSoft, USA). Differences were determined at the significance level of p ˂ 0.05. Results. ZC64-0001 increased the level of microcirculation relative to the group with modelled glaucoma by 11.5%, with this indicator being statistically significantly different from that both in the group with modelled glaucoma and the intact group ( р < 0.05). In the group of animals receiving ZC64-0001, the amplitude of a-wave increased relative to the primary glaucoma group by 17.7%, with this index being statistically different from the groups of intact animals and negative control (р < 0.05). The b-wave amplitude increased by 34.4% relative to the group with modelled glaucoma, being statistically different from the intact group, negative control group, pathology modelled group, and comparison drug groups ( р < 0.05). Administration of ZC64-0001 increased the number of retinal ganglion cell nuclei relative to the group with modelled glaucoma by 41.0%, which had a statistically significant difference from all the studied groups ( р < 0.05). Conclusion. The ZC64-0001 compound demonstrated high neuroprotective properties in a model of primary open-angle glaucoma, leading to an improvement in retinal microcirculation, an increase in the wave amplitude according to the conducted electrophysiological study, and an increase in the number of ganglion cell nuclei.

Background. Despite major progress in surgical care, the need remains to reduce the number of recurrences in the postoperative period in inguinal hernia patients and to improve their quality of life (QoL). To this end, the development of a technique for hernia repair, which would decrease dependence on the availability of consumables, appears promising. We present the surgical outcomes of inguinal hernia patients treated by the technique of tension-free hernioplasty using implants and auto-tissue flaps. Objective. To develop a technique for hernia repair with a reduced dependence on the availability of consumables, which could decrease the number of recurrences in the postoperative period in inguinal hernia patients and to improve their QoL indicators. Methods. An observational cohort study of 759 patients with inguinal hernias aged 18 years and older was conducted. The patients underwent treatment at the Ryazan City Clinical Hospital No. 11 and the Ryazan Region Clinical Hospital in the period from 2006 to 2022. The main group included 39 patients, who were operated by the Desarda technique modified by the authors. The modification consisted in the formation of a flap from the aponeurosis of the external oblique muscle, covering the seminal canal, with fixation of its free end to the inguinal ligament. The control group included 720 patients, 454 and 266 of whom were operated by the Bassini and Lichtenstein techniques, respectively. In order to evaluate the surgical outcomes, a comprehensive examination was performed, including collection of complaints, anamnesis, examination of the postoperative suture, and inguinal region. This included the size, shape, and hernia repairability, if any, dilation of the external inguinal ring, skin condition, painfulness and cough tremor at palpation, and ultrasound examination of the inguinal region. QoL was assessed using the SF-36 (Short Form) questionnaire. Statistical analysis was performed using the Statistica 13 software package (StatSoft, USA). Results. The patients of the main and control groups were divided into those who were admitted as planned and emergency patients. Long-term hernioplasty outcomes in the planned surgery patients were as follows: recurrences after the Desarda technique modified by the authors — 0 out of 24 (0.00%); recurrences after the Bassini technique — 44 out of 310 (14.20%); recurrences after the Lichtenstein technique — 7 out of 181 (3.87%). Long-term hernioplasty outcomes in the emergency patients were as follows: recurrences after the Desarda technique modified by the authors — 0 out of 15 (0,00%); recurrences after the Bassini technique — 31 out of 144 (21.53%); recurrences after the Lichtenstein technique — 4 out of 85 (4.70%). In the planned surgery patients of the main group, 5 QoL indicators were statistically significantly higher in relation to at least one method of hernioplasty of the control group. In the emergency patients, this number was 4 indicators. The absence of recurrences, both in planned and emergency patients, was associated with the non-invasiveness of auto-tissue, preserved non-tension, reduced dependence on the availability of consumables, and improved QoL of patients with inguinal hernias. These factors determine the advantages of the Desarda technique modification proposed by the authors. Conclusion. The application of the Desarda technique modified by the authors reduced the number of recurrences in the postoperative period in inguinal hernia in both planned surgery and emergency patients, improving their QoL. The suggested method of herniorrhaphy ensures reduced dependence on the availability of consumables.

Background. Gestational diabetes mellitus is the most frequent metabolic disorder during pregnancy. Its prevalence is steadily increasing worldwide. In the setting of hyperinsulinism, this pathology may cause various structural and functional changes in the placenta, as well as a reduction in oxygen supply to the fetus. This may result in fetal hypoxia and increased risk of fetal growth restriction. Therefore, research into the specific features of gestation course in patients with gestational diabetes mellitus in order to prevent its complications appears relevant. Objective. To study the specific features of gestation, delivery, and perinatal outcomes in patients with non-insulin dependent gestational diabetes mellitus. Methods. We conducted an observational cohort study of the case histories of 120 women with singleton pregnancies of the second and third trimesters with diagnosed non-insulin dependent gestational diabetes mellitus, their labor and delivery records, and the medical records of the newborns. All the patients were managed at the Ural Research Institute of Maternity and Child Care during 2021–2023. The main group comprised 70 patients whose pregnancy was complicated by sub- and decompensated forms of placental insufficiency. The comparison group comprised 50 pregnant women without pathologies of the fetoplacental complex. The obstetric history, gestation course of the present pregnancy and its outcomes, as well as the condition of the newborns, were analyzed. The obtained data were processed by the methods of variation statistics using Microsoft Excel spreadsheets (Microsoft, USA) and Statistica 13 (DellInc., USA) and MedCalc 15.8 (MedCalcSoftware, Belgium) applications. The null hypothesis was rejected at p > 0.05. Results. Gestational diabetes mellitus in previous pregnancies was statistically significantly less frequent in the main group (2.9% (n = 2)) than in the comparison group (18.0% (n = 9)) ( p > 0.05). Placental insufficiency in the main group was characterized by fetal growth restriction, which was associated with impaired uteroplacental blood flow in 58.6% (n = 41) of the cases. In the main group, the pregnancy ended in preterm delivery in 21.4% (n = 15) of the cases; in 78.6% (n = 55) of the cases, the delivery was at term. There were no preterm births in the comparison group, p > 0.05. Cesarean section was performed in 62.9% (n = 44) of patients in the main group, compared to 20.0% (n = 10) in the comparison group ( p > 0.05). Newborns of the main group required respiratory support more often (p > 0.05). Conclusion. The mechanism of placental insufficiency in patients with non-insulin dependent gestational disorders of carbohydrate metabolism remains to be elucidated. Further research should investigate the predictors of fetoplacental complex pathologies in this group of patients in order to reduce the number of perinatal complications.

Background. Visceral obesity is a risk factor in the development of metabolic and endocrine disorders leading to arterial hypertension and cardiovascular complications. Their early predictors include increased vascular stiffness and early vascular aging. The current literature lacks studies into the effects of changes in testosterone, cortisol, and aldosterone levels in serum on vascular stiffness and the development of early vascular aging in patients with visceral obesity. Objective. To determine the relationship between hypercortisolemia, hyperaldosteronemia, and hypotestosteronemia and vascular stiffness and the presence of early vascular aging in male patients with visceral obesity. Methods. An observational cohort study of 78 males aged 35–45 years (mean age 38.1 ± 6.5 years) diagnosed with abdominal obesity and grade 1 arterial hypertension was conducted. The mean waist circumference ranged 105.5 ± 6.9 cm; systolic and diastolic blood pressure ranged 152.5 ± 5.0 and 92.5 ± 5.0 mm Hg, respectively. The vascular age of the studied patients (n = 78) comprised 44.1 ± 6.2 years, which was statistically higher than their passport age (р < 0.001). The studied patients were divided into subgroups according to both total testosterone (< 12.1 nmol/l in subgroup 1A (n = 49) and ≥ 12.1 nmol/L in subgroup 1B (n = 29)) and cortisol in the evening saliva portion (> 4.5 nmol/L in subgroup 2A (n = 24) and ≤ 4.5 nmol/L in subgroup 2B (n = 24)). All the patients completed the study. To assess the hormonal status, the total testosterone sex steroid-binding globulin (SSBP) and insulin in morning serum samples were investigated. Insulin resistance was assessed based on the NOMA-IR index. The concentration of total testosterone was determined by enhanced chemiluminescence (Ortho-Clinical Diagnostics, J&J); the SSBP and insulin levels were determined by delayed fluorescence. Aldosterone content was determined by radioimmunoassay; free cortisol and testosterone were measured by luminescent LIA. Free and bioavailable testosterone concentrations in serum were calculated using an online calculator (issam.ch/freetesto.htm). The cardio-ankle vascular index (CAVI) was determined using a VaSera VS-15000N device, which automatically calculated the vascular age. Statistical analysis was performed using the Statistica 10.0 Windows package (StatSoft, Inc., USA). Results. The vascular age of patients with hypogonadism was statistically significantly ( р < 0.001) higher than their passport age and the vascular age in males without hypogonadism. The CAVI and vascular age were also statistically significantly higher in males with functional hypercorticism (р < 0.001) compared with a subgroup of patients without hypercorticism. The vascular age and CAVI increased with an increase in the salivary cortisol concentration 22⁰⁰ (r = 0.5; р < 0.05) and decreased with an increase in the salivary cortisol level 9⁰⁰ (r = –0.5; р < 0.05). These parameters decreased with an increase in serum aldosterone obtained in the morning (r = –0.4; p < 0.05) and increased with an increase in serum aldosterone in the evening (r = 0.4; p < 0.05). In 23% (n = 18), an inversion of the daily rhythm of cortisol production was observed; in these patients, salivary cortisol levels of 22⁰⁰ exceeded salivary cortisol levels of 9⁰⁰. The vascular age of patients with the inversion of cortisol production (49.4 ± 4.4 years) was statistically significantly ( р < 0.001) different from that of patients with normal changes in salivary cortisol concentrations (41.9 ± 4.9 years). CAVI was also higher (р < 0.001) in males with inverted fluctuations in salivary cortisol levels (7.51 ± 0.62) compared to those with normal diurnal rhythm (6.45 ± 0.69). The results of aldosterone evaluation revealed that 17% of the patients (n = 13) had higher aldosterone levels in the evening serum portion compared to the morning serum portion. In these patients, the vascular age (45.8 ± 5.1 years) was higher ( р < 0.001) than that in males with normal physiologic changes in aldosterone levels (41.6 ± 5.7 years). A similar pattern was observed when comparing vascular stiffness indices. Thus, the CAVI in men with inverted changes in aldosterone concentration (6.9 ± 0.8) was significantly higher ( р < 0.001), compared to that in men with physiological changes in blood aldosterone levels (6.4 ± 0.8). Conclusion. Endocrinologic disorders in male patients with visceral obesity and concomitant arterial hypertension (functional hypogonadism, functional hypercorticism, inverted daily rhythms of cortisol and aldosterone production) contribute to the development of early vascular aging by increasing vascular stiffness.

Background. Marshall syndrome, also known as the PFAPA syndrome, is an autoinflammatory disease characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This widely common pediatric autoimmune disease often remains undiagnosed due to a lack of knowledge about its clinical features. Therefore, it can be assumed that Marshall syndrome is much more common than it is diagnosed. We describe a clinical case of Marshall syndrome in a five-year-old boy by retrospectively analyzing the patient’s anamnesis, the course of the disease, the results of laboratory and instrumental studies. The treatment approach is also presented. Despite the complexity of this pathology, a positive result in the treatment of the child was achieved. Clinical case description. A five-year-old boy was admitted to the Cardio-Rheumatology Department of the Krasnodar Krai Children’s Regional Clinical Hospital for examination and clarification of the diagnosis. The patient’s parents complained of recurrent episodes of fever. During such episodes, the child’s blood tests revealed leukocytosis, increased erythrocyte sedimentation rate (ESR), and increased C-reactive protein levels. After the end of the episode, all indicators returned to normal levels. The anamnesis showed that, during the previous three months, the boy had been repeatedly hospitalized with various diseases. The preliminary diagnosis was “Juvenile arthritis, systemic variant. Autoinflammatory disease?”. Laboratory studies revealed antineutrophil cytoplasmic antibodies to proteinase-3 (cANCA), to myeloperoxidase (pANCA), and antinuclear antibodies (ANA) in a titer of 1/160. For differential diagnosis, genetic screening for familial Mediterranean fever was performed; however, no mutations in exons two, three, five, and ten of the MEFV gene were found. As a result, the child was diagnosed with “Autoinflammatory disease. Marshall syndrome.” The prescribed therapy with glucocorticosteroid drugs and immunosuppressants produced a positive effect. After recovery, the boy was discharged from the hospital under the supervision of a pediatrician at the place of residence. Conclusion. Difficulties in the treatment of such patients lie, first of all, in the verification of the diagnosis. Indeed, at early stages, the clinical symptoms of monogenic forms of autoinflammatory diseases and other diseases may be similar to Marshall syndrome. As a result, the patients are subjected to unnecessary massive antimicrobial therapy, resulting in deterioration of their quality of life for many years. Untimely diagnosis does not result in an unfavorable outcome or disability due to the benign clinical course of the disease.

Background. Acute flaccid paralysis is a clinical syndrome characterized by a sudden onset of weakness in one or more limbs with decreased or absent tendon reflexes in the affected limbs. This condition may be a manifestation of such pathologies as Guillain-Barré syndrome and neuromyelitis optica spectrum disorder. Clinical cases description. We describe two clinical cases of Guillain-Barré syndrome in patient M., 7 years old, and neuromyelitis optica spectrum disorder in patient D., 3 years old. In both children, the main clinical manifestation was acute flaccid paralysis. Patient M. was admitted to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection with complaints of sharp pronounced weakness in the limbs, inability to walk. According to the disease history, the patient had an acute respiratory viral infection in October 2022. The conducted neurologic examination revealed decreased muscle tone and muscle strength in all limbs, absence of reflexes from the lower limbs. A liquor test was conducted, which revealed increased protein contents. Electroneuromyography detected a pronounced axonal lesion of all motor fibers in the arms and legs. The formulated diagnosis was “Guillain-Barré syndrome, variant of acute motor axonal neuropathy.” The treatment with plasmapheresis and intravenous immunoglobulins showed positive dynamics. In the second case, patient D. was admitted to the Pediatric Infectious Disease Department of Naro-Fominsk Hospital with similar complaints of sharp weakness in the limbs. Neurological examination showed a diffuse decrease in muscle tone, absence of reflexes from all limbs. Elevated protein contents were determined in the liquor. MRI of the cervical spinal cord showed myelitis of segments C3–C7. Negative antibodies to aquaporin-4 were found. The patient was treated with ceftriaxone, methylprednisolone, and plasmapheresis. Then he was transferred to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection, where a repeated MRI of the cervicothoracic spinal cord revealed, in addition to myelitis at the level of C3–C7, a lesion of segments from the level of C2 to the medulla oblongata. The formulated diagnosis was “Neuromyelitis optica spectrum disease, seronegative form. Flaccid tetraparesis.” The continued treatment with prednisolone and intravenous immunoglobulin produced positive effect. Conclusion. The presented clinical cases will help neurologists to improve timely diagnosis and treatment of causes of acute flaccid paralysis in children, thereby reducing possible complications, disability, and mortality.