Hypochlorous Acid-Modified Serum Albumin Causes NETosis in the Whole Blood Ex Vivo and in Isolated Neutrophils.

Type 2 diabetes mellitus (T2DM) is accompanied by halogenative stress resulting from the excessive activation of neutrophils and neutrophilic myeloperoxidase (MPO) generating highly reactive hypochlorous acid (HOCl). HOCl in blood plasma modifies serum albumin (Cl-HSA). We studied the formation of neutrophil extracellular traps (NETs) in the whole blood and by isolated neutrophils under the action of Cl-HSA. It was found that Cl-HSA induces neutrophil priming and NETosis. MPO-containing as well as MPO-free NETs were found. These NETs with different composition can be a product of NETosis of one and the same neutrophil. NET formation in neutrophils with vacuolated cytoplasm was detected. In the presence of Cl-HSA, acceleration of NET degradation was observed. Accelerated NET degradation and neutrophil priming can be the factors contributing to the development of complications in T2DM.

Xenon Antiaggregant Effects.

In in vitro model of short-term therapeutic inhalation of Xe/O2 mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.

Clinical, Anamnestic, and Demographic Characteristics of Patients with Myocardial Infarction in Russian Federation According to the Russian Registry of Acute Myocardial Infarction - REGION-IM.

AIM: Based on data from the Russian REGION-MI registry, to characterize patients with myocardial infarction (MI) hospitalized in Russian hospitals, describe their historical, demographic, and clinical characteristics, and compare the results with the data of previous Russian and international registries of acute coronary syndrome. MATERIAL AND METHODS: REGION-MI is a multicenter prospective observational study. The follow-up period was divided into three stages: during the hospital stay, at 6 and 12 months after the inclusion in the registry. Demographic and historic data and information about the present case of MI were entered into the patient's individual record card. RESULTS: The median age of all patients was 63 years; 68% of patients were men. The mean age of women was older than that of men. Among all MI cases, 70% were ST-segment elevation myocardial infarction (STEMI). Patients with non-ST-segment elevation myocardial infarction (NSTEMI) were older and had more comorbidities than patients with STEMI. The median time from the first symptoms to ECG recording was two hours, and from the first symptoms to CAG 7 hours. CAG was performed in 91% of patients with STEMI and 84% of patients with NSTEMI. Stenting was performed in 69% of patients. Although many patients had a complicated cardiovascular history, at the time of admission only 31.5% of patients were taking at least one drug from the groups of antiplatelets, oral anticoagulants, statins, and beta-blockers. CONCLUSION: Patients with MI in the Russian Federation are younger than patients with MI in European countries. Among the clinical and historical characteristics, conspicuous is the presence of modifiable risk factors in many patients, as well as the presence of a previous diagnosis of ischemic heart disease. Furthermore, a small proportion of patients took statins, antiplatelet agents or anticoagulants at the outpatient stage, which indicates a great reserve of both primary and secondary prevention of cardiovascular diseases in the Russian Federation. The delayed seeking medical help is also noticeable, which indicates the need for increasing the public awareness of the symptoms of MI and the importance of timely hospitalization.

[Importance of parental compliance in postoperative rehabilitation of children with glaucoma]. / Znachenie komplaensa roditelei v reabilitatsii detei s glaukomoi v posleoperatsionnom periode.

One critical aspect of managing pediatric glaucoma is the compliance of parents, who are responsible for the care of their children. Achieving consensus between specialists and parents on the organization of comprehensive care is essential for the effective rehabilitation of young patients with glaucoma. PURPOSE: This study assesses the level of parental compliance with rehabilitation measures and attempts to identify the factors affecting it during the rehabilitation period of children after surgical treatment of congenital glaucoma. MATERIAL AND METHODS: The study was conducted through a survey involving 62 parents of children who underwent surgical treatment for glaucoma at the ophthalmology department of the Tashkent Pediatric Medical Institute. Parents were provided with a link to the online survey after giving their consent. The questionnaire consisted of eight questions with multiple-choice answers. RESULTS: Analysis of the answers showed the following trends: the majority of parents had either a secondary or vocational education (59.7%); most parents lived in rural areas (64.5%); a significant portion had partial or no knowledge about the course and outcomes of glaucoma (51.6%); unreliable sources for information (45.2%); irregular adherence to the doctor's recommendations (29%); significant difficulties in following the prescribed recommendations (64.5%). CONCLUSION: It was found that the level of parental compliance with rehabilitation measures is low in a significant portion of families (37.2%) with children who underwent surgery for glaucoma. The main factors contributing to poor parental compliance include living in rural areas, insufficient knowledge about the disease, lack of strict adherence to medical recommendations, and various difficulties in implementing the prescribed recommendations (p<0.05).

[The use of mineral trioxide aggregate for treatment of children with complications of dental trauma]. / Primenenie mineral trioksid agregata dlya lecheniya detei s oslozhneniyami travmy postoyannykh zubov.

THE AIM: Jf the study was to assess the efficacy of mineral trioxide aggregate for treatment of children with complicated permanent teeth trauma. MATERIAL AND METHODS: The study comprised 29 children aged 6-13 years (mean age 8.6±1.7 years) with 36 injured constant teeth, from which 30 had immature roots, 27 (75%) teeth had necrotic pulp at baseline examination, 12 (33.3%) teeth showed radiological signs of external imflammatory root resorbtion, 2 teeth were diagnosed with of the root fracture (5.6%). MTA was used for pulp regeneration procedure in 25 (69.5%) teeth, external closure of resorbtion site in 3 (8.3%) teeth, root canal filling in 4 (11.1%) teeth, apical plug creation in 4 teeth (11.1%). The patients were folowed up for 1 to 9 years. RESULTS: From 36 teeth only one was extracted 9 years after regenerative endodontic procedure because of cervical root fracture. In 2 teeth with external imflammatory resorbtion progession of replacement resorption took place, in 1 tooth necrosis of regenerated pulp tissue occurred 2 years after the procedure because of restoration marginal seal failure. In 25 teeth favorable outcome was registered with stabilisation of external root resorbtion, continous root growth in 24 teeth and radioluscent lesions healing in 6 teeht showing them at baseline examination. Change of external imflammator root resorbtion to replacement resorption was detected in 1 teeth from 3 with external closure of resorbtion site. Root calan filling with MTA was performed in 3 avulsed teeth with replantation delayed for more than 1 day and in 1 tooth with root fracture. All teeth were clinically asymptomatic during more than 5 years follow-up. Favorable outcome was received in all cases of apicl plug formation. CONCLUSION: MTA is highly effective for preservation of constant teeth in children with clinically complicated situations. In many cases with hopeless long-term prognosis for a teeth MTA allows stabilization of dental tissue level with the teeth being an object for guided tissue regeneration.

[Pulp revascularization procedure for external inflammatory dental root resorption treatment]. / Primenenie metodiki regeneratsii pul'popodobnoi tkani dlya ostanovki naruzhnoi vospalitel'noi rezorbtsii kornya zuba.

THE AIM OF THE STUDY: To assess the effectiveness of pulp revascularization procedure in children with external inflammatory root resorption (EIRR) after constant teeth injury. MATERIALS AND METHOS: The study comprised 17 children aged 6-10 years diagnosed with EIRR as a long-term complication of dental trauma in 19 teeth. EIRR was diagnosed with periapical radiographs and CBCT was performed to further assess the pathology extension. Pulp revascularization was carried out in all 19 teeth. RESULTS: There was no resorption progression in all cases. EIRR areas were substituted by bone. In 10 from 19 teeth with early stages of root development bone or cement-like tissue ingrowth into the root canal was observed radiologically. In cases of severe EIRR this ingrowth may partially compensate for lost tissues which is confirmed by a high percentage (94.7%) of functional teeth during mean follow up time of 38±10 months. CONCLUSION: Pulp revascularization is an effective method for retaining teeth with EIRR for a relatively long period of time and allows maintaining alveolar bone volume both due to functional tooth preservation and healing of bone lesions in periapical and resorption areas.

The Role of cAMP-Dependent Intracellular Signaling Pathways in the Regulation of the Functions of Neural Stem Cells and Neuroglial Cells in Amyloid-ß-Induced Neurodegeneration.

Under conditions of neurodegeneration modeled in vitro by the ß-amyloid peptide-(25-35) fragment (Aß25-35), we studied the role of individual links of cAMP-dependent intracellular signaling pathways in determining the proliferation and differentiation status of neural stem cells (NSCs) and colony-stimulating activity of supernatants from neuroglial cells. The important role of intracellular cAMP and PKA in the inhibition of the progression of the NSC cell cycle and stimulation of the process of their specialization induced by Aß25-35 was found. The selective ability of PKA to block the production of factors constituting colony-stimulating activity by neuroglial cells under conditions of their cultivation in vitro with a neurotoxic agent was revealed. Our results suggests that inhibitors of adenylate cyclase and PKA can increase the degree of implementation of the growth potential of NSCs and conjugation of the processes of their proliferation and differentiation in Alzheimer's disease. At the same time, selective PKA blockers can also induce the production of NSC-stimulating factors by neuroglial cells.

The Role of JNK and p53 in the Regulation of Secretory Function of Neuroglial Cells of Various Types in ß-Amyloid-Induced Neurodegeneration.

We studied the effect of JNK and p53 inhibitors on the production of neurotrophic factors stimulating the realization of the growth potential of neural stem cells by neuroglial cells of various types under conditions of simulation of induced ß-amyloid neurodegeneration in vitro. It was shown that ß-amyloid stimulates the production of neurotrophins by astrocytes and microglial cells, but does not affect the functioning of oligodendrocytes. JNK and p53 were not involved in the secretion of neurotrophins by intact astrocytes. The stimulating role of p53 on the implementation of their secretory activity under the influence of a neurotoxic agent was revealed. At the same time, the inhibitory role of JNK and p53 in the production of neurotrophic growth factors by oligodendrocytes and microglial cells was revealed both under conditions of their optimal vital activity and when ß-amyloid was added to the cell culture.

Effect of Paclitaxel on the Hemostatic Potential of the Blood in the Experiment.

The duration and severity of prothrombotic effects of the maximum tolerated dose of paclitaxel (40 mg/kg) were evaluated in intact outbred mice. Hemostasis was assessed before and on days 1, 2, 5, 7, 10, 15, 20, and 30 after a single injection of paclitaxel using standard coagulation tests (activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin III) and a "global" method, low-frequency piezothromboelastography. A pronounced prothrombotic effect of paclitaxel was revealed starting from the first day postinjection that consisted in intensification of fibrinogenesis up to the 7th day in parallel with activation of the anticoagulant mechanisms. On days 7-30 after paclitaxel administration, decompensation of its anticoagulant activity due to paclitaxel-induced damage to the endothelium was observed with the formation of a procoagulant status of the hemostatic potential of the blood. A single administration of the maximum tolerated dose of paclitaxel forms a powerful thrombogenic stimulus during the first week and provides a long-term/trace procoagulant shift in the hemostasis system (days 10-30).

The Effect of Vitamin D3 on Neutrophil Extracellular Trap Formation in High-Glucose Conditions.

NETosis, i.e., the formation of neutrophil extracellular traps (NET), and neutrophil autophagy are important elements in the pathogenesis and the development of complications of type 2 diabetes mellitus (T2DM). Therefore, the search of drugs that can regulate the level of NETosis and autophagy in T2DM is relevant. Here we studied an ex vivo NET formation and neutrophil death in whole blood from healthy subjects upon the addition of glucose up to a high concentration of 15 mM or/and the phorbol ester PMA (phorbol-12-myristate-13-acetate). Their individual and combined action caused neutrophil death and an increase in NET content. It can be hypothesized that this resulted from activation of NETosis and autophagy. It was also shown that this activation of NETosis and autophagy is completely prevented by daily intake of 1000 IU vitamin D3 for 14 days. Therefore, vitamin D3 supplementation can be considered as a preventive measure against the development of T2DM complications.

[Surgical treatment of aberrant subclavian artery]. / Khirurgicheskoe lechenie aberrantnoi podklyuchichnoi arterii.

OBJECTIVE: To determine the indications and optimal surgical treatment of aberrant subclavian artery. MATERIAL AND METHODS: There were 3 patients with aberrant subclavian artery with clinical manifestations such as dysphagia, shortness of breath, weight loss, cough and chest pain between 2005 and 2020. Right-and left-sided aberrant artery was observed in 2 and 1 case, respectively. Supraclavicular unilateral or bilateral access depended on the side of aberrant artery. Carotid-subclavian anastomosis was performed. RESULTS: All patients were discharged without any symptoms. CONCLUSION: Close location of aberrant subclavian artery to common carotid artery can disturb circulation in brain and upper limb. Abnormal discharge of subclavian artery can cause compression of nearby organs (esophagus, trachea). Abnormal vascular discharge does not always have clinical manifestations that do not require surgical correction. Only symptomatic patients are subjects to surgical correction of aberrant subclavian artery. Knowledge of variant anatomy of supra-aortic vessels can minimize the risk of complications.

[The results of the study of the focus of initial caries of human tooth enamel in vitro using atomic force microscopy]. / Rezul'taty issledovaniya ochaga nachal'nogo kariesa emali zuba cheloveka in vitro s pomoshch'yu atomno-silovoi mikroskopii.

OBJECTIVE: Identify structural disorders of the surface of the enamel of a human tooth during the development of the carious process in the «white spot¼ stage using atomic force microscopy (AFM). MATERIAL AND METODS: The studies were carried out on 10 molar samples in areas with initial caries in the white spot stage. 6 areas of initial caries were scanned using the atomic force microscope Cetus Light (Nano Scan Technology, Russia) in semi-contact mode. Criteria were proposed for comparing the results of AFM scanning of tooth enamel surface samples and, based on them, the nature of the main structural disorders of the enamel surface in the affected area was determined. RESULTS: For all the samples studied, the healthy enamel surface was smoother compared to the enamel in the area of the clinically visible «white spot¼ and in the immediate vicinity of it. The heterogeneity of the enamel surface in the center of the white spot¼ for all the samples studied was at least 60% higher than at the edge of the process. It was revealed that the heterogeneity of the surface outside the clinically visible white spot at a distance of less than 1 mm from its perimeter is at least 30% higher than that of healthy tissue of the same tooth. It is shown that the heterogeneity of the enamel surface in the center of the caries area in the white spot stage is at least 4 times greater than the heterogeneity of the surface of the healthy enamel of the same tooth, which indicates its demineralization. CONCLUSION: The established features of the spread of the initial carious process can be used in clinical practice for the diagnosis and dynamic observation of the processes of enamel demineralization.

Expression of NLRP3 Inflammasomes in Neurogenic Niche Contributes to the Effect of Spatial Learning in Physiological Conditions but Not in Alzheimer's Type Neurodegeneration.

A common feature of neurodegenerative disorders, in particular Alzheimer's disease (AD), is a chronic neuroinflammation associated with aberrant neuroplasticity. Development of neuroinflammation affects efficacy of stem and progenitor cells proliferation, differentiation, migration, and integration of newborn cells into neural circuitry. However, precise mechanisms of neurogenesis alterations in neuroinflammation are not clear yet. It is well established that expression of NLRP3 inflammasomes in glial cells marks neuroinflammatory events, but less is known about contribution of NLRP3 to deregulation of neurogenesis within neurogenic niches and whether neural stem cells (NSCs), neural progenitor cells (NPCs) or immature neuroblasts may express inflammasomes in (patho)physiological conditions. Thus, we studied alterations of neurogenesis in rats with the AD model (intra-hippocampal injection of Aß1-42). We found that in Aß-affected brain, number of CD133+ cells was elevated after spatial training in the Morris water maze. The number of PSA-NCAM+ neuroblasts diminished by Aß injection was completely restored by subsequent spatial learning. Spatial training leads to elevated expression of NLRP3 inflammasomes in the SGZ (subgranular zones): CD133+ and PSA-NCAM+ cells started to express NLRP3 in sham-operated, but not AD rats. Taken together, our data suggest that expression of NLRP3 inflammasomes in CD133+ and PSA-NCAM+ cells may contribute to stimulation of adult neurogenesis in physiological conditions, whereas Alzheimer's type neurodegeneration abolishes stimuli-induced overexpression of NLRP3 within the SGZ neurogenic niche.

Melting of crystallites in a solid porous matrix and the application limits of the Gibbs-Thomson equation.

A thermodynamic model is proposed to describe the melting of lamellar crystallite in a solid medium. This model includes a modification of the Gibbs-Thomson equation to make it applicable to the above-mentioned crystallites. The need for such modification is supported experimentally by studying the impact of the surroundings on the melting point of the crystallites. In particular, the application of the model to nanocrystals in open-porous systems makes it possible to determine the analytical relations for the melting point, the heat of melting, and the inverse effective size of the pores. The fitting of the experimental data with these functional relations then allows for the calculation of the nanocrystalline density, pressure in the nanocrystal, and difference in the surface tension coefficients at the nanocrystal-matrix interface and melt-matrix interface, as well as the difference in the surface entropies per unit area at the nanocrystal-matrix and melt-matrix interfaces.

Functional State of Various Types of Regenerative-Competent Neural Tissue Cells in ß-Amyloid-Induced Neurodegeneration.

We analyzed the content and functional activity of various types of regenerative-competent cells of the subventricular zone of the cerebral hemispheres in experimental mice under conditions of in vitro modeling of ß-amyloid-induced neurodegeneration. Fundamentally different (opposite) effects of ß-amyloid on functional activity of multipotent neural stem cells (NSC) and neuronal committed progenitors (NCP) were revealed. ß-Amyloid suppressed proliferation of NSC and stimulated their differentiation. At the same time, an increase in the mitotic activity of NCP was observed with a decrease in the intensity of their specialization. These changes in the functioning of progenitor cells developed against the background of a significant drop in the production of neurotrophic growth factors by neuroglia. These phenomena indicate marked discoordination of the activity of regenerative-competent cells of various types.

Megakaryocytes of the Spleen in Experimental Amyloidosis and Effect of Red Wine.

Amyloidosis was modeled in young mice by administration of aqueous solution of soy cream substitute and then, amyloidogenesis was corrected by oral administration of dry red wine. In mice with amyloidosis, the area of megakaryocytes decreased by 1.69 times, the relative content of oxyphilic forms of megakaryocytes increased by 4.33 times, and ploidy did not change in comparison with the corresponding parameters in intact mice. Administration of red dry grape wine against the background of formation of systemic amyloidosis changed the reaction of megakaryocytes: the content of polychromatophilic forms was comparable to the level of intact control, the content of oxyphilic forms decreased by 3.11 times, the RNA and DNA content in megakaryocyte nuclei decreased proportionally, and the ploidy decreased. Thus, red grape wine reduced the response of the megakaryocyte genome to the external supply of amyloidogenic substance.

The Role of JAKs and STAT3 in Regulation of Regenerative-Competent Cells of the Nervous Tissue in ß-Amyloid-Induced Neurodegeneration.

We studied the role of JAKs and STAT3 in the growth potential of neural stem cells and the humoral neurotrophic function of neuroglia in modeling ß-amyloid-induced neurodegeneration in vitro. It was found that these signaling molecules do not participate in the neural stem cell functioning, and JAKs plays an inhibitory role (realized, however, without STAT3) in the secretion of neurotrophins by glial cells under conditions of their optimal vital activity. The effect of ß-amyloid on progenitor cells is accompanied by the appearance of a "negative" effect of STAT3 signaling pathway on their proliferative activity. At the same time, JAKs and STAT3 during neurodegeneration stimulate specialization/differentiation of neural stem cells and production of growth factors by neuroglial cells. These results indicate the possibility of stimulating proliferation of neural stem cells coupled with their differentiation by using selective STAT3 inhibitors.

The Role of MARK ERK1/2 and p38 in Regulation of Functions of Neural Stem Cells and Neuroglia under Conditions of ß-Amyloid-Induced Neurodegeneration.

The role of ERK1/2 and p38 in the realization of the growth potential of neural stem cells and secretion of neurotrophic growth factors by glial cells was studied using in vitro model of ß-amyloid-induced neurodegeneration. It was shown that amyloid-ß fragment 25-35 significantly inhibits the cell cycle progression of neural stem cells against the background of stimulation of their differentiation and reduced production of growth factors by neuroglia. The inhibitory role of ERK1/2 and p38 in relation to the proliferative activity of neural stem cells and the secretory activity of glial elements was revealed. ERK1/2 and p38 inhibitors increased proliferation of progenitor cells of the nervous tissue and reduced the intensity of their specialization, as well as stimulated production of growth factors by neuroglial cells under conditions of simulated ß-amyloid-induced neurodegeneration.

Postpartum Involution of Mouse Myometrium in Acute CCl4-Induced Hepatosis and Its Correction with Immobilized Hyaluronidase.

We studied structural rearrangement of the myometrium of C57BL/6 mice during the postpartum period under conditions of acute toxic hepatosis induced by CCl4 injection and its correction with immobilized hyaluronidase. In contrast to physiological pregnancy, involution of the myometrium in mice under conditions of acute toxic hepatosis were not completed by the 10th day of the postpartum period. When toxic hepatosis was corrected with immobilized hyaluronidase, the main mechanism of postpartum involution of the mouse myometrium was clasmacytosis, the process of postpartum involution was significantly accelerated, but not completed by the 10th day, probably due to reduced vascularization of the myometrium.

[Potential risk factors of atrial fibrillation recurrence after cryoballoon ablation].

Aim      To identify risk factors for recurrence of atrial fibrillation (AF) following cryoballoon ablation (CBA).Material and methods  This prospective study included patients with paroxysmal AF who had undergone CBA (141 patients, median age 60 years, 3% men). The evaluation prior to CBA included clinical instrumental parameters (electrocardiography (ECG), 24-h ECG monitoring, echocardiography, contrast-enhanced cardiac multispiral computed tomography). Also, possible intraoperative indexes that could affect the CBA effectivity, were evaluated. The postoperative follow-up duration was 12 months. Effectivity was assessed during in-person visits at 3, 6, and 12 months, when questioning of patients and 24-h ECG monitoring were performed. CBA was considered ineffective if the patient had recurrences of any atrial tachyarrhythmia longer than 30 sec after the end of the 3-month "blind" period.Results During the 12-month follow-up, recurrences of atrial tachyarrhythmia were observed in 46 (32.6 %) patients. Patients with ineffective CBA more frequently had AF during the first 3 months (71.7 % vs. 11.6 %; р<0.001). Such patients had a history of multiple ineffective treatments with antiarrhythmic drugs (AAD), common pulmonary venous (PV) collector (41.3 % vs. 20.0 %; р=0.008), and stroke/recurrent ischemic attacks (15.2 % vs. 5.2 %; р=0.047). Multifactorial regression analysis showed that the factors of AF recurrence included common PV collector (relative risk (RR) 2.35; 95 % confidence interval (CI) 1.29-4.25; р=0.005), multiple ineffective AADs (RR 1.42; 95 % CI 1.08-1.86; р=0.011), and early AF recurrence (RR 7.57; 95 % CI 3.84-14.90; р<0.001).Conclusion      Common PV collector and multiple ineffective AADs are risk factors of ineffective CBA. Early recurrences during the first 3 postoperative months are a significant risk factor of long-term AF recurrences.