[Characteristics of histochemical, molecular genetic and radiation-induced liver changes depending on the postmortem interval]. / Kharakteristika gistokhimicheskikh, molekulyarno-geneticheskikh i luchevykh izmenenii pecheni v zavisimosti ot davnosti smerti.

The aim of this study is to analyze literature data on postmortem changes in the liver and their use in determination of postmortem interval. Biological death expectedly causes the development of postmortem disorders not only in the liver structure, but also changes in its biochemical and histochemical parameters. Literature data about changes of histochemical, immunohistochemical and biomolecular characteristics of liver tissue, as well as bacterial migration to the liver depending on the duration of postmortem period, are presented. The effectiveness of radiology for visualization of postmortem changes and, accordingly, for determining the postmortem interval is noted.

[Characteristics of structural morphological changes of the liver depending on the prescription of death coming]. / Kharakteristika strukturnykh morfologicheskikh izmenenii pecheni v zavisimosti ot davnosti smerti.

The purpose of the work is to analyze the literature data devoted to the study of postmortem morphological changes in liver tissue and their use to determine the prescription of death. Postmortem changes are based on the processes of postmortem redistribution of blood and autolysis, the speed and severity of development of which depends primarily on the lifetime pathology, as well as external temperature and humidity during storage of the corpse. The onset of biological death naturally entails the development of postmortem changes in the liver, manifested by a decrease in temperature, violations of the structure of organelles, cells and organ tissue as a whole. The determination and evaluation of developing postmortem morphological changes is necessary both for differential diagnosis with lifetime-developed pathological processes, and for determining the prescription of death coming. This necessitates research to study the features of the development of postmortem changes and to develop ways to assess them to determine the prescription of death coming.

[Postmortem assessment of cerebral edema]. / Posmertnaya otsenka oteka golovnogo mozga.

An analysis of literature data on the methods of post-mortem assessment of cerebral edema is presented. Based on the mechanisms of development, two main types of cerebral edema are distinguished: cytotoxic (intracellular) and vasogenic (extracellular). To determine cerebral edema, a number of methods are used, both direct and indirect, invasive and non-invasive assessment. Direct methods for assessing cerebral edema are based on determining the amount of water in its tissue. Indirect methods include morphological and radiation studies. Traditionally, the most evidence-based criteria for the diagnosis of cerebral edema are macroscopic and microscopic changes determined at autopsy. Methods are also indicated for determining the content of water in brain tissue by comparing the mass of wet and dry brain, as well as estimating the specific density of brain tissue.

Regulation of the Placental Renin-Angiotensin-Aldosterone System in Early- and Late-Onset Preeclampsia.

Preeclampsia (PE) is one of the most dangerous complications of pregnancy, characterized by hypertension, proteinuria, and symptoms of multiple organ failure, which are detected de novo after 20 weeks of pregnancy. The renin-angiotensin-aldosterone system (RAAS) is one of the first to recognize pregnancy and is an important regulator of blood pressure. The placenta has its own RAAS, the role of which in the development of PE is not fully understood. In this work, for the first time, we characterized the expression of RAAS components and miRNAs controlling it in the placenta at various times of PE manifestation. The data obtained will allow the development of a new strategy in the future for the search for therapeutic agents for patients suffering from PE and cardiovascular diseases.

The Role and Place of Thanatoradiological Studies in the Pathological Examination of Fetuses and Newborns.

Analysis of published data on the possibilities of using postmortem radiation studies in perinatology is carried out and the results of own thanatoradiological studies of the bodies of dead fetuses and newborns are presented. The possibilities of postmortem radiation studies for differential diagnosis of stillborn and deceased newborns, evaluation of the severity of maceration and the time of intrauterine fetal death, detection of pathological changes in the brain and spinal cord, respiratory and digestive organs, in the cardiovascular and urinary systems were demonstrated. It is concluded that postmortem CT has a high diagnostic efficiency in the study of the bone skeleton, free fluid accumulations in serous cavities and gas in the vessels and tissues of dead fetuses and deceased newborns. The advantage of postmortem MRI is more effective visualization of internal organs and soft tissues, which allows assessing their topography and size, as well as identifying a wide range of pathological changes. For a comprehensive objective analysis of the bodies of stillborn and deceased newborns, combined use of both imaging methods (CT and MRI) is required. At the same time, thanatoradiology should be used as a part of a comprehensive pathological study, but not as a substitute for traditional autopsy.

Comparative Characteristics of Sialoglycans Expression Disorders in the Placental Barrier Structures in Preeclampsia and Fetal Growth Restriction.

We compared the expression profiles of α2,3- and α2,6-sialoglycans in the glycocalyx of the placental barrier structures in early and late forms of preeclampsia and fetal growth restriction using the method of lectin histochemistry. It was found that the expression of α2,3-sialoglycans in the syncytiotrophoblast and fetal endothelium of the terminal villi of the placenta was reduced in preeclampsia in comparison with normal placenta and, on the contrary, was increased in fetal growth restriction. Significant differences were found in both clinical phenotypes of preeclampsia and fetal growth restriction. Changes in the expression pattern of α2,6-sialoglycans in the endothelium of terminal villi were more pronounced than in syncytiotrophoblast. In early and late-onset preeclampsia, a significant increase in the expression of α2,6-sialoglycans was revealed only in the fetal endothelium; in early fetal growth restriction, the expression of α2,6-sialoglycans was reduced in the endothelium, but increased in syncytiotrophoblast in late fetal growth restriction. The features of the expression of sialoglycans in structures of the placental barrier in preeclampsia and fetal growth restriction were revealed, which may indicate the pathogenetic involvement of sialoglycans in the inflammatory activation cascade in fetal growth restriction, and in preeclampsia, apparently, they are associated with impaired fetal tolerance.

Comparative Characteristics of the Expression of Fucosylated Glycans and Morphometric Parameters of Terminal Placental Villi Depending on the Severity of Preeclampsia.

We performed a comparative analysis of the expression of fucosylated glycans and morphometric characteristics of the terminal villi of the placenta, depending on the severity of preeclampsia (PE). Similar patterns of the expression of fucosylated glycans in the syncytiotrophoblast glycocalyx were revealed in the placental tissue of patients with normal pregnancy and with mild and severe PE: predominance of glycans with α1,6-fucose in the core, clustered fucose residues, and LeX glycan over α1,2-fucose-containing glycans. The expression pattern of fucosylated glycans and the composition of the endothelial glycocalyx are normally close to the expression pattern and composition of the syncytiotrophoblast glycocalyx; in case of mild and severe PE, the expression pattern of fucosylated glycans was changed uniformly, and α1,2-fucose-containing glycans significantly prevailed in the endothelial glycocalyx. According to the results of Fisher's LSD test, in patients with severe PE, the total vascular area in the villus prevailed over the indices established during physiological course of pregnancy (p=0.04) and mild PE (p=0.04). Correlation analysis revealed direct and reciprocal relationships between the morphometric characteristics of the terminal villi of the placenta and the expression of fucosylated glycans in the syncytiotrophoblast and endothelium in PE. Our results indicate a changed expression of fucosylated glycans in the glycocalyx of placental barrier structures and the morphometric parameters of villi in PE of different severity, which can affect the function of the placental barrier.

Morphometric Parameters of Placental Villi in Parturient Women with COVID-19.

We performed a comparative morphological analysis of placental villi in parturient women with mild and moderate COVID-19 infection. The area and perimeter of terminal villi, their capillaries, and syncytiotrophoblast were assessed on immunohistochemical preparations with antibodies to CD31 using an image analysis system; the parameters of fetal vascular component in the placental villi were also assessed. Changes in the studied parameters differed in parturient women with mild and moderate COVID-19 infection. The observed increase in the total perimeter with a simultaneous decrease in the total capillary area and the degree of vascularization of the placental villi in parturient women with COVID-19 indicates impairment of circulation in the fetal compartment and the development of placental hypoxia, which can be the cause of unfavorable neonatal outcomes.

The Number of Syncytial Knots and VEGF Expression in Placental Villi in Parturient Woman with COVID-19 Depends on the Disease Severity.

A comparative morphological study was carried out to analyze the number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 categorized by the disease severity. The number of syncytial knots was assessed on specimens stained with hematoxylin and eosin. VEGF expression was determined by immunohistochemical analysis in syncytiotrophoblast and villous endothelial cells. Morphological study of the placenta tissue of parturient women with COVID-19 showed increased numbers of syncytial knots in the villi, indicating the development of preplacental hypoxia. High VEGF expression in syncytiotrophoblast and vascular endotheliocytes reflects a stereotyped response to hypoxia and can underlie the development of a preeclampsia-like syndrome. The number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 depended on the disease severity.

The Use of Atomic Force Microscopy in Comprehensive Assessment of the "Mother-Placenta-Fetus" System in Obstetric and Endocrine Pathology during Pregnancy.

Atomic force microscopy is not very popular in practical health care, therefore, its potential is not studied enough, for example, in obstetrics when studying the "mother-placenta-fetus" system. Our study summarizes the possibilities of using atomic force microscopy for detection of various circulatory disorders and vascular changes at the microscopic level in the uterus (endometrium and myometrium), placenta, and umbilical cord in the main variants of obstetric and endocrine pathology. For instance, in the case of endocrine pathologies, changes in the form of stasis, sludge, diapedesis, ischemia, destruction and separation of endotheliocytes in villous blood vessels were found in the mother. The oxygen content in erythrocytes also naturally decreased in pathologies; poikilo- and anisocytosis were observed.

[Technical and methodological support for postmortem radiation examinations in the pathological departments and the forensic bureau]. / Tekhnicheskoe i metodicheskoe obespechenie provedeniya posmertnykh luchevykh issledovanii v patologoanatomicheskikh otdeleniyakh i byuro sudebno-meditsinskoi ekspertizy.

The purpose of the work is to analyze the technical and methodological features of postmortem radiation studies based on literature data and the results of our own experience. To designate such studies, the term thanatoradiology has been proposed. The basis for the effective conduct of a thanatodiological examination is adequate technical support, which equally consists of the capabilities of the equipment for obtaining radiographs, CT and MR tomograms (type and generation of the device, technical features of a particular model), as well as the capabilities of the radiologist's workstation with the help of which the computer processing of the obtained images is carried out, three-dimensional reconstructions are performed, the calculation of planar and volumetric parameters and additional information is obtained. The use of an X-ray unit allows one to assess only pronounced pathology and the presence of foreign objects. The effectiveness of a computed tomography device depends on the choice of the slice thickness and the step of the examination table. Research on a magnetic resonance imager is effective at certain magnetic induction strength, the form of a magnetic coil and the used mode of recording a pulse sequence. The objectivity and efficiency of digital processing of tomograms consists of the type of a radiologist's workstation and installed programs for post-processing tomograms, including for modeling three-dimensional images and color mapping. The choice of a specific method of postmortem radiation research should be determined mainly by the research objectives. Research should be carried out taking into account age, body weight, individual characteristics and the state of body tissues. Today, it is advisable to use radiation methods as part of a comprehensive pathological and anatomical or forensic medical research to improve the quality and shorten the autopsy duration. The development of a unified protocol for postmortem CT and MRI studies that meets the pathological, anatomical and forensic requirements remains an urgent task.

[Organization of postmortem radiological examination in the structure of pathological departments and forensic bureaus]. / Organizatsiya provedeniya posmertnykh luchevykh issledovanii v strukture patologo-anatomicheskikh otdelenii i byuro sudebno-meditsinskoi ekspertizy.

The purpose of this work is to develop an optimal scheme for organizing and conducting postmortem radiation studies in the Russian Federation based on literature data and our own results. One of the primary points in organizing virtopsiy is to determine the place where radiation examinations of deceased patients will be performed. The absence or presence of the equipment and capabilities available in the institution, i.e., the department of radiation diagnostics with functioning CT and MRI devices and software, determines the volume of economic costs. The analysis of the results of radiation research methods should be carried out by a highly qualified radiologist who has both general knowledge of radiation diagnostics and information about the radiation pattern of nonspecific postmortem changes. Based on our own experience in organizing postmortem radiation examinations, we consider it optimal to conduct postmortem CT and/or MRI scans by an X-ray technician in the radiation diagnostics department and to introduce a separate radiologist in the staffing of the pathology department or forensic medical examination bureau. In our opinion, an examination of the corpse by a radiologist in conjunction with a forensic expert is required to determine the most important areas of interest, tactics and methodology of radiation research. The final conclusion of the radiologist should be formed after consultation and agreement of the identified changes with a pathologist or forensic expert. Virtopsy is a highly effective objective method for examining a corpse. This dictates the need for its widespread introduction into the practice of the forensic medical examination bureaus and pathological and anatomical departments.

Postmortem MRI Characterization of Cadaveric Hypostases in Deceased Newborns.

Using postmortem MRI, we studied the features of the development of internal cadaveric hypostasis in dead newborns. Postmortem radiological and pathoanatomical examination of 62 bodies of newborns and infants who died at the age of 1.5 h to 49 days was carried out. After the death was ascertained, prior to MRI, the bodies were stored in a refrigerator at 4°C in the supine position. Depending on the duration of the postmortem period (2-72 h), all observations were divided into eight groups. Prior to autopsy, an MRI scan was performed in T1 and T2 standard modes, followed by analysis of the presence and severity of the gradient line of the intensity of the MR signal in the liver and lung tissue in the ventral (overlying) and dorsal (underlying) areas, as well as the presence of a gradient of the intensity of the blood signal in the heart cavity and in the aortic lumen. The main manifestations of cadaveric hypostasis in the liver and lungs are changes of the MR signal intensity in the ventral and dorsal regions with the appearance of a horizontal gradient of the MR signal intensity, which reflects the location of the body after death. In the heart cavity and in the aortic lumen, there is also a gradient of the blood signal intensity of various severity with the visualization of two or three of its layers. The revealed features of the MRI signal intensity and, accordingly, the presence of its horizontal gradient depended not only on the MRI mode of the study, but also on the studied organ and the duration of the postmortem period. This should be taken into account when analyzing the results of virtopsy and determining the links of thanatogenesis of dead newborns and infants.

Postmortem Computed Tomography Angiography of Newborns.

We propose an original method of postmortem computed tomography angiography of the body of a deceased newborn. The work is based on the analysis of the results of comprehensive postmortem computed tomography and pathological examination of 30 newborns, who died from congenital malformations. The key to a full-fledged postmortem radiation study using intravascular contrasting of deceased newborns and infants is the presence of vascular catheters established during life, as well as conducting it no earlier than 12 h and no later than 48 h after death. As a contrast agent, we recommend to use an iodine-containing water-soluble radiopaque drug containing at least 250 mg of iodine per 1 ml. The volume of contrast agent is calculated based on body weight, taking into account the general edema syndrome. The introduction of a contrast agent is carried out through vascular catheters in 3 stages in various positions of the body. The analysis of tomograms and 3D-reconstruction of blood vessels using their pseudocoloring allows accurate assessment of the topography of blood vessels with the possibility of separate study of the arterial and venous vessels, and to identify both congenital abnormalities of the heart and blood vessels, and their acquired pathology. CT angiography in some cases is superior to traditional autopsy in the diagnosis of blood vessel pathology. Postmortem CT angiography should be considered as an important stage of postmortem radiology in the structure of comprehensive pathological analysis of newborns and infants.

Postmortem MRI Evaluation of Maceration Degree of Deceased Fetus.

We studied the possibilities of postmortem MRI for assessing the degree of maceration and determining the duration of intrauterine fetal death. Postmortem radiological and pathoanatomic study of the bodies of 38 stillbirths who died antenatally (main group, n=31) and intranatally (control group, n=5), who were born at gestational periods of 22-40 weeks was performed. Before the autopsy, MRI was performed in standard T1 and T2 modes. The tissue of the liver, kidney, brain, femoral muscle, lung, and skin in the hip, abdomen, and skull were studied on T1- and T2-weighted images (WI), followed by calculation of the of MR signal intensity ratio in T2- and T1-WI (SIR). The duration of intrauterine fetal death was determined based on the results of autopsy and analysis of histological preparations. It was found that the calculated values of SIR depended on the evaluated organ and the duration of intrauterine fetal death. Unfortunately, the revealed dynamics of changes in SIR does not allow unambiguous assessment of the severity of maceration processes and, accordingly, the time of fetal death due to its non-linear nature. Nevertheless, the use of SIR indicators of several organs and areas of the body makes it easier to determine the duration of intrauterine fetal death and, hence, to clarify the links of thanatogenesis of the stillborn. The advantages of post-mortem MRI compared to autopsy include non-invasive nature of the study, the possibility of archiving and subsequent multiple delayed analysis of tomograms, as well as the speed of MRI analysis, in contrast to microscopic stage of pathological examination associated with the need to prepare histological preparations.

Complex Method of CT and Morphological Examination of Placental Angioarchitechtonics.

We propose an original method of complex assessment of the placental angioarchitechtonics based on computed tomography (CT) and morphological examination. A prerequisite condition of successful examination and assessment of the placental angioarchitechtonics is the pre-preparative stage including clearing of the placental and umbilical cord vessels from blood clots by placement of placenta into 10% hypertonic NaCl solution and then on a hygroscopic substrate. The major stage of this method is injection of contrast staining mixtures into the umbilical vessels followed by CT. The concentration of radiocontrast agent in water solution of gouache should be 70% for arteries and 15% for veins. The volumes of mixtures for contrast staining should be calculated according to the weight of the placenta. The contrast staining mixture was first injected into the catheterized unpaired umbilical vein, and then into both umbilical arteries. Each injection of the contrast staining mixture was visually inspected; then branching of the stained vessel was photographed and scanned by CT. The CT scans were used to construct 3D models of placental vessels and spectral color maps, which made it possible to examine the peculiarities of placental angioarchitechtonics, to identify and evaluate anastomoses of placental vessels, and to establish the type of these anastomoses.

Telocytes in the Myocardium of Children with Congenital Heart Disease Tetralogy of Fallot.

Telocytes, a new type of interstitial stem cells with long thin processes that form a three-dimensional network around cardiomyocytes, vessels, and nerve fibers were described in the myocardium of children with tetralogy of Fallot. Two types of morphologically different telocytes, spindle-shaped and rounded, were identified. Contacts of telocytes with stem cells and interstitial macrophages were found. Telocytes were more common in the immature myocardium, where the assembly of myofibrils in cardiomyocytes was not completed and small Ki-67+ cardiomyocyte progenitor cells were present. Telocytes expressed immunohistochemical markers CD117, vimentin, CD34, and CD44. Localization and ultrastructural characteristics of telocytes suggested their participation in stem cell differentiation, coordination of neoangiogenesis, and paracrine regulation of all components of the interstitium.

Expression of fucosylated glycans in endothelial glycocalyces of placental villi at early and late fetal growth restriction.

The aim of the study was to investigate the content and distribution of fucosylated sugar residues and Lewis Y (LeY) in the endothelial glycocalyx (eGC) in placental tissue at early and late onset fetal growth restriction (FGR). Our findings demonstrated that the changes of the fucosylated glycans of type 2 (H2)/LeY in the vascular endothelium of the villi may reflect alteration of villi maturation, or adaptation to hypoxia through the change of cell proliferation potential and induction angiogenesis. Early onset FGR differs from late onset FGR by a markedly increased LeY expression, being associated with more severe pathological state.

Enhanced Expression of TLR8 in Placental Tissue in Preeclampsia.

The expression of TLR8 in the placental tissue was studied in specimens from women of reproductive age with early- and late-onset preeclampsia (12 and 8 patients, respectively). The reference groups included 15 women: 10 with uneventful full-term pregnancy and 5 with preterm operative delivery on gestation weeks 28-33. The expression of TLR8 in placental structures was maximum in early-onset preeclampsia (p<0.01) characterized by the gravest clinical course, while the expression of TLR8 in late-onset preeclampsia was comparable with that in full-term pregnancy. This significant increase of TLR8 expression in placental tissue seemed to reflect activation of the key proinflammatory factors of congenital immunity and induction of the systemic inflammatory response. Manifest differences in the expression of TLR8 in late- and early-onset preeclampsia confirmed the hypothesis on different variants of this condition.

Peculiarities of RIG-1 Expression in Placental Villi in Preeclampsia.

The expression of RIG-1 in placenta samples was assessed in women of reproductive age with early- and late-onset preeclampsia and cesarean delivery at 27-39 weeks of gestation. The highest expression of RIG-1 was found in the syncytiotrophoblast of placental villi in the group with uncomplicated full-term pregnancy (normal); RIG-1 expression in groups with early- and late-onset preeclampsia was significantly (p<0.01) lower. In decidual cells, RIG-1 expression was also maximum in normal pregnancy and significantly (p<0.01) lower in lateonset preeclampsia. In the endothelium of villous capillaries, the maximum expression was observed in normal full-term pregnancy and in late-onset preeclampsia, while in early-onset preeclampsia this parameter was significantly (p<0.01) lower. It can be assumed that different variants of preeclampsia are mediated by similar pathogenetic mechanisms, including those related to immature molecular profile of the trophoblast and decidual cells, probably due to impaired stem cell activity in the placenta determining higher vulnerability and reduced regeneration capacity of the placental tissue. This is due to the fact that RIG-1 is one of the important signaling molecules that promote activation of stem cell and tissue regeneration.