


Vol 162, No 3 (2024)
- Year: 2024
- Published: 15.12.2024
- Articles: 10
- URL: https://j-morphology.com/1026-3543/issue/view/9231
- DOI: https://doi.org/10.17816/morph.20241623
Original Study Articles
The role of connexin 43 in remodeling cardiomyocyte intercellular contacts in hypertrophic cardiomyopathy
Abstract
BACKGROUND: Intercellular gap junctions play a special role in the biology of cellular interactions. Their structural and dispositional changes can affect some biological functions, including disruption of electrical pulse propagation, which is primarily important for myocardial function.
AIM: The aim was to evaluate the morphological characteristics and localization of connexin 43-containing (Cx43+) gap — junctions and to determine their association with changes in myocardial morphology of the interventricular septum and clinical parameters in patients with hypertrophic cardiomyopathy.
MATERIALS AND METHODS: Morphometry and immunohistochemistry of interventricular septal myocardium were performed in patients with hypertrophic cardiomyopathy (n = 62, aged 18 to 61 years) compared with subjects without cardiovascular disease (n = 8, aged 25 to 54 years). Resection of the interventricular septum of the right ventricle was performed in patients with hypertrophic cardiomyopathy. Cx43+ gap junctions were identified in cardiomyocytes and their location and ultrastructural arrangement were determined. The data obtained were compared with clinical parameters of patients with hypertrophic cardiomyopathy.
RESULTS: In the interventricular septal myocardium of patients with hypertrophic cardiomyopathy, a redistribution of Cx43+ gap junctions from intercalated discs to the lateral surfaces of cardiomyocytes was observed. Gap junction changes are more frequent and more extensive in patients with hypertrophic cardiomyopathy than in the control group. They are typical of patients with the most severe morphological and functional cardiac condition, as evidenced by echocardiographic data such as significant thickening of the interventricular septum and a decrease in the volume of the left ventricular cavity. Morphologically complex remodeling of the myocardium is manifested by hypertrophy of the cardiomyocytes and partial loss of their myofibrils. Ultrastructurally, 28.1% of patients with hypertrophic cardiomyopathy had gap junction defects in the myocardium such as sites of localized divergence of intercalated disc membranes and abnormal ring structures formed by invaginations of gap junction-containing sarcolemma.
CONCLUSION: The location of Cx43+ gap junctions on the lateral surfaces of cardiomyocytes and changes in their ultrastructure suggest cardiomyocyte immaturity of the interventricular septum, which is typical of patients with hypertrophic cardiomyopathy and may cause a disruption of the electromechanical coupling of the myocardium.



Seasonal changes in absolute and relative organ weight in 3-month male Wistar rats
Abstract
BACKGROUND: To correctly interpret preclinical studies and basic research, it is necessary to accurately assess the biometric parameters of normal status and their limits. Biometric parameters of animals of genetically pure lines are known to vary according to factors such as sex and age, but little attention is paid to a seasonal factor. Therefore, it seems relevant for physiology and pathophysiology to develop reference values of normal status and their limits for working with genetically pure animals during certain periods of ontogenesis and different seasons.
AIM: The aim of the study was to determine the absolute body and organ weights and the relative organ weights of adult male Wistar rats at three months of age during different seasons of the year.
MATERIALS AND METHODS: The experiment involved 160 male Wistar rats. The animals were divided into four groups so that the rats reached the age of three months in one of the seasons: spring, summer, fall, or winter. In each group, absolute and relative body and organ weights were measured for the brain, spleen, thymus, liver, kidneys, adrenal glands, heart, lungs, and testes.
RESULTS: The most significant seasonal differences were found in the absolute weights of all organs, while the relative weight coefficients of the organs differed in only 50% of the cases. Synchronous seasonal differences in kidney and adrenal gland weights were observed. The heart was found to have the most significant seasonal variability in both weight parameters studied.
CONCLUSIONS: The absolute organ weight is one of the most sensitive parameters in determining reference values, but changes in the relative weight coefficient should also be considered. This study established reference ranges for the weight of major organs in a population of healthy, genetically homogeneous Wistar rats at three months of age and showed seasonal variations in these reference ranges. Further research is needed to understand changes in organ weights combined with pathological data.



Anatomy of the inferior pyramidal space tendon in the fetal and neonatal heart: a pilot study
Abstract
BACKGROUND: Knowing the anatomical features of the inferior pyramidal space tendon of the fetal and neonatal heart (the tendon of Todaro, TT) is important for perinatal cardiac surgery (e.g., with access to the left atrium), but has been virtually unstudied.
AIM: The aim of the study was to evaluate the possibility of dissecting and evaluating the TT macromicroscopically and to obtain preliminary data on its presence, shape, size, branching and local topography in the fetal and neonatal heart.
MATERIALS AND METHODS: Fifteen samples of normal human hearts at 16–40 weeks of gestation were examined. Ten hearts were dissected under an Olympus SZX2-ZB10 microscope (Olympus, Japan) at a magnification ranging from 6.3 to 30×. The length and width of the TT were measured using a Levenhuk M1000 PLUS camera (Levenhuk, Russia) with a resolution of 10 Mpx and Levenhuk lite software. The arithmetic mean, standard deviation, median, extreme values, coefficient of variation and Spearman correlation coefficient (Rs) were calculated. Histologic sections were prepared from five hearts and stained using the Masson trichrome technique.
RESULTS: The TT was detected in all specimens and was always located in the intramyocardial space and/or in the loose connective tissue of the inferior pyramidal space. In all cases, the TT was originated from the right fibrous triangle, anterior to and above the atrioventricular bundle and node, where the TT was most monolithic. The TT then followed between the inferior border of the patent foramen ovale and the opening of the coronary sinus, ending at the valve of the inferior vena cava. In 6 out of 10 cases, the TT had no branches. In 4 out of 10 cases, it divided into two branches covering the opening of the coronary sinus. The TT fibers reaching the right coronary artery were dissected in one specimen. The median width of the TT at the inferior vena cava valve (0.35 mm) correlated with its length (4.63 mm; Rs = 0.821; p = 0.023) and width at the origin (0.24 mm; Rs = 0.929; p = 0.0003).
CONCLUSIONS: The inferior pyramidal space tendon of the heart in the late prenatal and perinatal period of human development is characterized by variable anatomy and constant topography. Variable structure is manifested by variations in tendon branching, a wide range of lengths and especially widths. Constant topography means that the tendon originates, runs, and ends in the same places. This tendon can be identified in fetal and neonatal hearts using macromicroscopic dissection.



New data on landmark anatomy of the human superior thyroid artery
Abstract
BACKGROUND: The description of anatomy of the thyroid vasculature is widely used in both traditional medical literature and modern research. However, authors note variability in locating the superior thyroid artery orifice relative to the common carotid artery bifurcation. However, there is no standard approach to determining the linear dimensions of the common carotid bifurcation zone. In this context, it is important for both morphologists and clinicians to determine the position of the superior thyroid artery orifice in relation to various anatomical landmarks.
AIM: The aim of the study was to identify variations in the location of the superior thyroid artery orifice relative to the common carotid artery bifurcation, the superior edge of the thyroid cartilage, and the superior edge of the thyroid lobe as landmarks.
MATERIALS AND METHODS: The study used 36 neck organ complexes obtained at autopsy from individuals without apparent thyroid disease using an original technique developed by the authors. The organ complexes were dissected, the arterial pool was injected with a colored gelatin-based compound, and the specimens were fixed. Photographs of the specimens were analyzed using a superimposed coordinate grid with a step size of 5 mm.
RESULTS: Most commonly, the upper edge of the common carotid artery bifurcation was found at the level of the upper edge of the thyroid cartilage on the right side and below it on the left side. It was also located above the upper edge of the corresponding thyroid lobe bilaterally. The superior thyroid artery orifice was most commonly located in the area of the common carotid artery bifurcation bilaterally. A moderate direct correlation was found on the right side between the location of the superior thyroid artery orifice and the upper edge of the bifurcation relative to the upper edge of the thyroid cartilage (Rs = 0.402, p < 0.05). There was also a direct strong relationship between the location of the superior thyroid artery orifice relative to the upper edge of the thyroid lobe and the length of the artery on the right side (Rs = 0.826, p < 0.05).
CONCLUSIONS: The study confirms the literature data regarding the variability of the superior thyroid artery location. The data obtained suggest that it is useful to use landmarks that can be easily determined during surgery to identify the location of the superior thyroid artery orifice.



Comparative features of thymus morphology in human and vertebrate animals (Chordata, Vertebrata)
Abstract
BACKGROUND: It is well known that the thymus structure in the vertebrate phylogeny is characterized by a combination of conservative and highly plastic features. However, the question remains about the causes and patterns of evolutionary similarities and differences in human and animal thymus structure depending on level of organization, habitat, and adaptability.
AIM: The aim of the study was to identify the main patterns of change in the thymus microscopic structure in phylogeny by comparing the thymus structure in humans and various Chordata species.
MATERIALS AND METHODS: Light microscopy was used to determine the cortical/medullary and mitotic indices as well as the area of fibrous tissue, lymphoid tissue, and adipose tissue in thymus sections from 19 vertebrate species and humans. Thymocytes, thymic corpuscles, and the number and area of microcirculatory vessels were counted per conventional area unit. The study was conducted on immature animals of each species as well as on animals that had reached the second stage of maturity.
RESULTS: Comparative analysis shows that immature animals have predominantly similar thymus structures. Significant differences were observed in the parameters of age-related involution, which is characterized by significant magnitude and total fat degeneration in humans compared to animals. The morphological features of the thymus associated with thymocyte migration and maturation have the highest conservatism and include cortical/medullary and mitotic indices, the numerical density of thymocytes in the cortex, the total area of microcirculatory vessels, the relative area of lymphoid tissue. Human thymus, regardless of age, has a higher relative amount of fibrous tissue than vertebrates. In addition, some specific morphological features of the thymus corpuscles also vary.
CONCLUSIONS: The structural features of the human thymus were determined that changed in adaptation to specific conditions of the anthropogenic environment. The revealed morphological differences in human thymus are consistent with immunological hypothesis explaining the causes of age-related thymic involution. They correspond to the main points of Academician A.A. Zavarzin’s theory of parallel development of homologous tissues in vertebrate phylogeny.



Bone tissue status in early stages of recovery after thermal exposure
Abstract
BACKGROUND: Thermal ablation is a promising method for the treatment of bone tumors. However, to maximize the potential of this method, it is important to select the optimal dose/time ratio of high temperature exposure.
AIM: The aim of the study was to evaluate in vivo the response of rabbit bone tissue during early recovery (days 3 and 7) after local intraoperative hyperthermic ablation at 55–60°C in the medullary canal.
MATERIALS AND METHODS: The study used 6 outbred rabbits aged 15 weeks and weighing 3–4 kg. Animals were removed from the experiment on days 3 and 7 after local thermal ablation of the femoral diaphysis. Microscopic visual examination of bone tissue sections was performed after standard hematoxylin and eosin staining. In addition, the morphometric measurements were performed to determine area of non-mineralized bone matrix (Mallory staining); absorbance and area of osteoblast cytoplasm; absorbance and area of osteocyte nuclei (Einarson staining for nucleic acid detection). The results obtained were compared with those of the femur of the contralateral limb, which was not subjected to direct hyperthermia and served as a control. R-Studio, a free development environment for R programming language, was used to statistically process the data.
RESULTS: After high temperature exposure, histological sections of bone tissue stained with hematoxylin and eosin showed evidence of cellular abnormalities such as denucleated osteocytes and empty bone lacunae. Mallory staining showed no evidence of a negative effect of local thermal ablation on the intercellular bone matrix. Morphometry of Einarson stained sections showed an increase in osteoblast area on day 7 after exposure, with a decrease in their synthetic activity, signs of which were observed as early as day 3 of the experiment. There was also a decrease in the area and absorbance of osteocyte nuclei in the diaphysis of thermally ablated bones by day 3 after exposure. However, on day 7 after exposure, the area of nuclei in mature bone cells did not differ from the corresponding value in the contralateral limb. Considering the decrease in nuclei absorbance, the described changes may indicate colliquative necrosis of osteocytes.
CONCLUSIONS: Local intraoperative thermal ablation of the femoral diaphysis in rabbits at a marrow canal temperature of 55–60℃ reduces the absorbance of osteoblast cytoplasm and osteocyte nuclei in the early recovery period, reflecting damage to the organelles of bone cells and disruption of metabolic processes in these cells. However, there was evidence of remodeling of the damaged area, presumably caused by migration of endosteal and periosteal cells from the metaphysis, which had not been exposed to direct hyperthermia. The results obtained may be useful for choosing the optimal regime (dose and duration) of high temperature exposure to bone tissue tumors, given the higher sensitivity of malignant cells to heating.



Sex differences in systemic inflammatory response in hypoxia-resistant Wistar rats
Abstract
BACKGROUND: Individual differences in hypoxia tolerance and hypoxia-inducible factor 1 alpha (HIF-1α) expression were identified in humans and laboratory animals. This was the basis for identifying groups of animals with low and high hypoxia tolerance. Animals with low hypoxia tolerance are known to have a more severe course of systemic inflammatory response (SIR). Sex differences in the severity of SIR in low hypoxia-tolerant animals have not been studied.
AIM: The aim was to evaluate sex differences in the severity of lipopolysaccharide (LPS)-induced SIR in Wistar rats with low hypoxia tolerance.
MATERIALS AND METHODS: Low hypoxia-tolerant animals were determined by their survival time in a hypobaric chamber under conditions equivalent to 11,500 m altitude (less than 60 s). The SIR was modeled by intraperitoneal administration of LPS at 1.5 mg/kg. Morphological changes in the lungs, liver, and thymus, as well as serum levels of endotoxin, corticosterone, HIF-1α, and TGF-β, were evaluated in males and females after 24 hours.
RESULTS: In control groups of low hypoxia tolerant rats, higher serum levels of HIF-1α, corticosterone and endotoxin were found in females compared to males. Compared to females, males usually have a higher thymic cortical volume fraction and lower subcapsular thickness. When LPS was administered to low hypoxia-tolerant females and males, sex differences in the severity of SIR were revealed. For example, in females, 24 hours after LPS administration, the neutrophil count in pulmonary interalveolar septa was higher, and random thymic involution with subcapsular zone narrowing developed without changing cortical volume fraction. Males demonstrated large abnormal lesions in the liver and more significant manifestations of accidental involution with a decrease in thymic cortical volume fraction. Serum corticosterone levels increased in females with SIR, and HIF-1α and endotoxin levels increased and TGF-β levels decreased in males.
CONCLUSION: LPS-induced SIR and immune responses in low hypoxia-tolerant Wistar rats depend on sex.



Morphologic features of synaptic structures associated with human cortical amyloid plaques
Abstract
BACKGROUND: Progressive and irreversible synaptic loss is a key manifestation of Alzheimer’s disease (AD) that correlates with the degree of AD-associated cognitive impairment. The study of synaptic impairment may be necessary to understand the AD development and progression. Therefore, it seems important to analyze structural and functional changes in synapses during the development of this disease. Synaptophysin, a synaptic vesicle membrane protein, is one of the most reliable and widely used synaptic markers in such studies.
AIM: The aim of this study was to investigate the morphological characteristics of synaptophysin-containing structures in the human cerebral cortex during amyloid plaque formation.
MATERIALS AND METHODS: The study used cerebral cortex samples (n = 10) from men and women between the ages of 65 and 94 years. A new and original technique for light microscopy based on immunohistochemical detection of synaptophysin and staining of amyloid plaques with Alcian Blue was used for the simultaneous detection of synapses and amyloid plaques.
RESULTS: In most amyloid plaques, abnormal synaptophysin-immunopositive structures were found, presumably representing dystrophic presynapses. These structures were characterized by large size and diffuse shape and were found exclusively in amyloid plaques. It should be mentioned that polysaccharide bodies (corpora amylacea) were detected in all samples of the cerebral cortex, characterized by a distinct spherical shape and located predominantly near the meninges, periventricularly and perivascularly. Synaptophysin-immunopositive terminals surrounding polysaccharide bodies had a typical structure and distribution density in all cases and showed no signs of abnormality.
CONCLUSIONS: In the cerebral cortex of elderly, senile, and long-lived individuals with AD, abnormal synaptophysin-containing structures form within or around amyloid plaques. Further study of these structures promises to identify new biomarkers of synaptic disorganization, including AD and early diagnostic markers for AD.



Editorial
Programmed cell death: new nomenclature
Abstract
There are several professional societies around the world that are dedicated to finding and systematizing new information about programmed cell death. In 2018, the International Nomenclature Committee on Cell Death (NCCD) published the latest revision of the cell death nomenclature. Since then, the 2023 update of the consensus document on apoptosis has been published. The International Society of Cell Death (ICDS) has identified new trends in studying this important step in cytogenesis and histogenesis. The aim of this report is to present new information on the nomenclature of programmed cell death types, their classification, and the scientific and practical significance of the new findings to a national audience of experts.



Исторические статьи
Zakhar Katsnelson — outstanding Russian histologist
Abstract
The article is a tribute to Zakhar Katsnelson, who was a brilliant histologist, a great teacher, and a man of extraordinary integrity and morality. Zakhar Katsnelson became famous as one of the founders of broad comparative descriptive and experimental research of embryonal histogenesis. The authors of this article were interested in his personality, first of all, because he was their compatriot, born in the small Ural town of Irbit. The article provides biographical information about Katsnelson’s scientific career and outlines his professional activities. The most important of Katsnelson’s theoretical and practical scientific researches are described, such as the analysis of effects of chemical factors on the embryonic and larval development of amphibians, the study of the embryonic development of the suprarenal glands in farm artiodactyls, including the demonstration of the inadequacy of the capsule blastema theory and the proof of cell dimorphism in the suprarenal medulla, etc. Katsnelson’s role in cytological research in the USSR is highlighted. Special attention is paid to his participation in the campaign against the pseudoscientific concept of O.B. Lepeshinskaya, which contradicts the cell theory of R. Virchow. The article describes professor Katsnelson’s pedagogical and methodological activities and his talent as a teacher. The article reviews his works on teaching methodology and the history of morphology, which still play an important role in educating veterinary and medical students.


