Assessment of the Level of Matrix Metalloproteinases, VEGF and MicroRNA-34a in Patients With Non-obstructive and Obstructive Lesions of the Coronary Arteries.

AIM: To assess the levels of matrix metalloproteinases (MMP), vascular endothelial growth factor (VEGF), and miRNA-34a expression in patients with ischemic heart disease (IHD) and obstructive and nonobstructive coronary artery (CA) disease. MATERIAL AND METHODS: This cross-sectional observational study included 64 patients with IHD (diagnosis verified by coronary angiography or multislice computed tomography coronary angiography), of which 33 (51.6%) were men aged 64.9±8.1 years. 20 patients had nonobstructive CA disease (stenosis <50%), and 44 had hemodynamically significant stenoses. The control group consisted of 30 healthy volunteers. MMP-1, -9, -13, and -14, miRNA-34a, and VEGF were measured in all patients. RESULTS: The concentration of MMP-1 was significantly higher in patients with ischemia and nonobstructive CA disease (INOCAD) (p=0.016), and the concentration of MMP-9 was the highest in the group with obstructive CA disease (p<0.001). The concentrations of MMP-13 and MMP-14 did not differ significantly between the groups. The highest VEGF concentrations were observed in the INOCAD group (p<0.001). The expression of miRNA-34a significantly differed between the IHD groups with different types of CA disease and controls (p <0.001). Patients with hemodynamically significant stenosis showed moderate relationships between the concentrations of MMP-14 and VEGF (ρ=0.418; p=0.024), as well as between VEGF and miRNA-34a (ρ=0.425; p=0.022). Patients with INOCAD had a significant negative correlation between the concentrations of MMP-13 and VEGF (ρ= -0.659; p=0.003). Correlation analysis showed in all IHD patients a moderate relationship of the concentrations of MMP-1 and MMP-14 with VEGF (ρ=0.449; p=0.002 and p=0.341; p=0.019, respectively). According to ROC analysis, a MMP-9 concentration above 4.83 ng/ml can be a predictor for the presence of hemodynamically significant CA obstruction in IHD patients; a VEGF concentration higher than 27.23 pg/ml suggests the absence of hemodynamically significant CA stenosis. CONCLUSION: IHD patients with INOCAD had the greatest increase in MMP-1, whereas patients with obstructive CA disease had the highest level of MMP-9. According to our data, concentrations of MMP-9 and VEGF can be used to predict the degree of CA obstruction. The expression of miRNA-34a was significantly higher in IHD patients with INOCAD and CA obstruction than in the control group, which suggested a miRNA-34a contribution to the development and progression of coronary atherosclerosis. In the future, it may be possible to use this miRNA as a diagnostic marker for IHD.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.

Aim      To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods  Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion      This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.

Comparative analysis of tryptophan and downstream metabolites of the kynurenine and serotonin pathways in patients with arterial hypertension and coronary artery disease.

Aim    To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD).Material and methods    This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer.Results    Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5­hydroxyindoleacetic acid (5­HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5­HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. Conclusion    Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5­HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.

[Takayusu Arteritis on the background of congenital vascular anomaly?]

The article described a female patient with high-grade arterial hypertension diagnosed at her young age. Congenital abdominal aortic hyperplasia and conformity with criteria for Takayasu arteritis were diagnosed at 10 years following the clinical manifestation.

[Perfusion-metabolic interaction in acute cerebral insufficiency. ACIPS study Part I. Cerebral blood flow evaluation].

Basic physiological position that metabolic requirements of brain determine perfusion characteristics of cerebral blood flow underlies the definition of syndrome of acute cerebral insufficiency. So there is a perfusion-metabolic interaction (PMI) in brain tissue at every moment. Based on this paradigm we should synchronize measurement of these components in intensive care practice. The goal of ACIPS study (Acute Cerebral Injury Protection System) is creating methodology of monitoring PMI and treatment algorithm based on this monitoring. In this article we present data that volume cerebral blood flow can be assessed by summing volume bloodflows on brachiocephalic vessels measured with triplex ultrasound. Such results are comparable with CT-perfusion results. Both methods can be used interchangeably if difference in -0.6-11.8 ml/kg/min isn't clinical significant.

Comparison of seasonal dynamics of the essential PUFA contents in benthic invertebrates and grayling Thymallus arcticus in the Yenisei river.

Seasonal dynamics of contents of essential polyunsaturated fatty acids (PUFA) in dominant groups of benthic invertebrates: gammarids (Gammaridae, Amphipoda), oligochaetes (Oligochaeta), chironomid larvae (Chironomidae, Diptera) and caddisfly larvae (Trichoptera), and dominant benthivorous fish, Siberian grayling Thymallus arcticus, have been studied in ecosystem of the large Siberian river. During the year of the study most benthic invertebrate taxa showed significant variations in the contents of both C-18 and long chain C-20-22 PUFAs. In contrast, the fish, which consumed the zoobenthos, had no significant seasonal variations in long chain PUFAs' contents. Thereby, the fish, as organisms of relatively higher evolution level than invertebrates, was supposed to have more strict metabolic control of long chain PUFAs' contents. Evidence was obtained that the studied fish species, grayling, may be capable to convert dietary EPA into DHA.

[Variant radiation anatomy of the lacrimal sac at visualization by contrast-free computed tomography].

OBJECTIVE: to morphometrically estimate normal variations in the sizes of lacrimal sacs on the basis of computed tomography findings to optimize the choice of endoscopic surgical intervention tactics for dacryocystitis. MATERIAL AND METHODS: Preoperative orbital computed tomography data were comparatively morphometrically processed in two groups of patients with or without clinically verified dacryo- cystitis. RESULTS: Data on the typical variants of the sizes of the lacrimal sac in health and in clinically manifested dacryocystitis were obtained and statistically processed. The advantages of using the design volume of the lacrimal sac over other measurements were shown. A method for the morphometry of lacrimal sacs was proposed on the strength of computed tomography data. CONCLUSION: The obtained new refined data on the holotopy of the lacrimal sac in health and clinically verified dacryocystitis can simplify the choice of an approach to planning endonasal dacryocystorhinostomy.

[Use of a method of staining sections with methyl green-pyronine for histobacterioscopic purposes]. / Ob ispol'zovanii metodiki okraski srezov metilovym zelenym-pironinom v gistobakterioskopicheskikh tseliakh.

A method of staining of histological sections with methyl green-pyronine for histobacterioscopic detection of microflora in tissues is proposed. A bright red staining with pyronine of microbial agents and yeast-like fungi of the genus Candida due to a high content of RNA in them permits elective detection of their insignificant amounts in tissues even at low magnifications of the microscope.

[New type of wound infection and sepsis caused by the marine vibrio V. vulnificus]. / Novyi vid ranevoi infektsii i sepsisa, vyzyvaemykh morskim vibrionom V. vulnificus.

A review is presented on the new type of infection produced by V. vulnificus and manifested by a wound infection and sepsis. Geographical distribution, routes of infection and clinico-anatomical manifestations are described. The importance of liver damage and conditions followed by the increase of the iron content in the blood for the development of V. vulnificus sepsis are evaluated.

[Amyloidosis of the pancreatic islets and diabetes mellitus]. / Amiloidoz ostrovkov podzheludochnoi zhelezy i sakharnyi diabet.

Pancreas was examined in 136 patients who died at the age of 7 to 89 years of various diseases including 22 with diabetes mellitus. Amyloidosis of its islands was observed in 9 patients (aged 49 and over); 6 out of them suffered from diabetes mellitus. Number of islands with amyloidosis and amyloid quantity were determined morphometrically. Glucagon-producing A-cells and insulin-producing B-cells in the islands not involved in amyloidosis were counted in sections impregnated by Grimelius. It is found that the development of diabetes is determined not only by the islands amyloidosis but by the quantitative domination of A-cells over B-cells in the islands without amyloidosis as well being the manifestation of aging processes.

[T- and B-lymphocytes. Distribution in the body, their functional and morphological characteristics and significance]. / T-i B-limfotsity. Raspredelenie v organizme, funktsional'no morphologicheskaia kharakteristika i znachenie

In a survey of the literature special attention is given to the history of development of concepts concerning the existence in the immunocompetent system of the lymphoid tissue of higher vertebrals and man of two independent to some extent populations of lymphocytes: one dependent on the thymus gland and therefore called T-lymphocytes population, implementing cellular reactions of immunity; and the other, similar one, dependent on Fabricius' bursa in birds and called B-lymphocytes, producing antibodies circulaing in the blood. Functional-morphological characteristics of T-and B-lymphocytes, their distribution in the peripheral organs of the lymphoid system and in the blood are given. The role of T-and B-lymphocytes in rejection of allotransplants and in the reaction of a transplant against the host development of reactions of hypersensitivity of the delayed and immediate types is discussed. The need for a further study of participation of T-and B-lymphocytes in pathogenesis of allergic, autoimmune and numerous other diseases that are accompanied by immune disorders, is emphasized.

[Infectious complications of leukemias and other tumors of the hematopoietic system]. / Infektsionnye oslozhneniia leikozov i drugikh opukholei krovetvornoi sistemy.

In 1975-1982, autopsies of 201 patients dying with leukemias and other tumors of hemopoietic system revealed infectious complications in 68.6%, among them pneumonias in 46.8%, sepsis in 10.9%, and inflammatory-necrotic processes of the digestive tract in 19.4%. More frequent occurrence of infectious complications in acute leukemias (68-75%) as compared with chronic (61-70%), in lympholeukemias (70-75%) as compared with myeloleukemias (61-68%), and virus infections including generalized forms of herpes in lymphogranulomatosis (30.8%) was noted. The importance of immunodeficiency conditions and granulocytopenia in the development of infectious complications which were the immediate cause of death of 56.7% of those dying with leukemias and other tumors of the hemopoietic system is discussed. The increased role in the etiology of these complications of the opportunistic intestinal microflora frequently present in various associations and in combinations with other microbes and fungi is noted.

[Patterns in the lesions of different sections of the hemopoietic system in leukemia]. / Nekotorye zakonomernosti porazhenii razlichnykh otdelov krovetvornoi sistemy pri leikozakh.

Morphological examinations of the hemopoietic system in 43 patients died of different forms of leukemias revealed irregular involvement into the leukemic processes of its different parts. Differences in the spread of leukemic lesions in the spleen, lymph nodes, tonsils and other lymphoid formations in lympho- and myeloleukemias were demonstrated. They are discussed from the point of view of the concept on metastatic involvement of different parts of the hemopoietic system in leukemias and on the importance in the development of these lesions of the cellular microenvironment. Also, the importance of atrophic changes of the thymus and other lymphoid structures as manifestations of immunological insufficiency which is one of the most significant conditions for the development of leukemia is discussed.

[Hypersensitive reactions and their significance in human pathology. Autoimmune diseases]. / Reaktsii giperchuvstvitel'nosti i ikh znachenie v patologii cheloveka. Autoimmunnye bolezni.

In the light of current concepts on cell interactions in hypersensitivity reactions of the cell-mediated and humoral type the author analyses morphological manifestations of these reactions, the possibility of change of one type of the reaction by the other in the course of immunopathological process, and the importance of hypersensitivity reactions in the development of many human diseases. According to the Sell's scheme, six groups of such diseases differing from each other by the pattern of the immunopathological mechanisms underlying them are considered. The importance of pathological investigations which would reveal characteristic local morphological manifestations in the forms of various types of immune inflammation and changes in the organs of the immunocompetent system of the lymphoid tissue, which could be used for judgement of the pattern and essence of the immunopathological process, is emphasized.

[Pathological anatomy and the pathogenetic problems of acute pneumonias of varying etiology]. / Patologicheskaia anatomiia i nekotorye voprosy patogeneza ostrykh pnevmonii raznoi étiologii.

Acute pneumonias comprise a group of infectious diseases of different etiology which determines many features of clinico-anatomic manifestations of some of their forms including the extension of inflammatory lesions in the lungs. Usually developing due to disorders in the draining function of the bronchi, disorders of the phagocytic activity of leukocytes and alveolar macrophages as well as the presence of immunodeficient conditions, acute pneumonias emerge as complications of other diseases. From 1962 to the present time the rate of their detection in fatal cases increased from 11.6% to 42.8%. Their most frequent causative agents are staphylococci resistant to most antibiotics used for treatment, less frequently Pseudomonas aeruginosa and pathogenic fungi. Also, an increased role in the etiology of pneumonias of conditionally-pathogenic flora (Proteus, Acinetobacter, Enterobacter, Serratia) and frequent pneumonias caused by mixed microflora are observed. Pneumonias were the immediate cause of death in 19.2% of the fatal cases.

[Legionnaires' disease (etiology, epidemiology, morphology and pathogenesis of "legionnaires" disease)]. / Legionellezy (etiologiia, epidemiologiia, morfologiia i patogenez "bolezni legionerov").

A review of the world literature on the "Legionnaires' disease", an infectious disease which was designated in 1979 as "legionellosis" and described in three different clinicoanatomic forms is presented. These forms differ both in manifestations of the disease and in species of the causal agents, legionellae, united in a genus Legionellaceae. Particular attention in the review is paid to morphological lesions observed in legionelloses (macro- and microscopic, and ultrastructural). The necessity of a careful histobacterioscopic examination of tissues in suspected cases of legionellosis and additional crucial bacteriological and serological examinations is noted. Since in the majority of the observations the main pathological process was represented by pneumonia (pleuropneumonia with frequent abscessing), the main differential diagnostic features of legionellosis pneumonia and its differences from other similar infectious diseases are described.

[Xanthogranulomatous cholecystitis]. / Ksantogranulematoznyi kholetsistit.

The morphologic changes are described found in the gallbladder of a female patient, aged 40; she had xanthogranulomatous cholecystitis secondary to cholelithiasis combined with a hiatal hernia and multiple duodenal diverticulae (Saint's triad).

[Pathological anatomy of present-day sepsis]. / Patologicheskaia anatomiia sovremennogo sepsisa

Analysis of prosector's findings and results of pathoanatomical studies of 65 cases who had died from sepsis showed that its incidence increased from 0.92% in 1956--1960 to 4.11% in 1971-1974. Along with the well-known typical manifestations of sepsis, a number of its perculiar features associated with application of modern therapeutic methods are considered: the prevailing form of sepsis is pyemia (81.5%), considerable incidence of sepsis following peritonitis and septic thrombophlebitis developing at sites of prolonged catheterization of veins. The significance of staphylococci and Bacillus pyocyaneus, which are resistant to the majority of the available at present antibiotics, as principle pathogenes of modern sepsis is emphasized. A dependence between the localization and size of metastatic foci and the kind of pathogene and nature of its toxines is noted. Among the conditions contributing to the development of sepsis the authors consider a reduction of the immunological reactivity of the organism morphologically characterized in the dead persons studied by the absence in lymphatic follicles of lymphatic nodes and the spleen, of "light" centres, drastic atrophic changes in the thymus gland in the majority of cases, and by slightly manifested phenomena of phagocytosis of microbes in the foci of inflammation. The role of operative and other traumas, the character of preceding diseases and application of immunodepressive therapy in the reduction of the immunological reactivity of the organism is tressed.

[Clinico-anatomic characteristics of sepsis caused by polymicrobial flora]. / Kliniko-anatomicheskaia kharakteristika sepsisa, vyzyvaemogo polimikrobnoi floroi.

Pathological examinations of 23 fatalities due to sepsis caused by polymicrobial flora revealed in 7 cases polymicrobial flora in metastatic foci of dissimilar composition in different foci, in 4 cases monomicrobial flora but varying in different foci, in 12 cases monomicrobial flora similar in all examined septic foci despite the presence in the blood of two or more agents. Localization of metastatic septic foci to a certain extent dependent on the nature of the sepsis causative agents comprising the association. Polymicrobial forms of sepsis were found in fatal cases due to leukemia in 50.0%, to burn sepsis in 10.8%, and to other diseases in 2.8% of the cases, indicating the dependence of their development on the degree of reduction of immunological responsiveness of the patients. The effect of antibacterial therapy given to the patients on the etiology of sepsis is discussed.