Background and Objectives: The coronavirus (SARS-CoV-2) damages all systems and organs. Yet, to a greater extent, the lungs are particularly involved, due to the formation of diffuse exudative inflammation in the form of acute respiratory distress syndrome (ARDS) with next progression to pulmonary fibrosis. SARS-associated lung damage is accompanied by the pronounced activation of mononuclear cells, damage of the alveoli and microvessels, and the development of organized pneumonia. To study the expression of macrophage markers (CD68 and CD163), angiotensin-converting enzyme-2 (ACE2), and caspase-3 on the results of two fatal clinical observations of COVID-19. Materials and Methods: In both clinical cases, the female patients died from complications of confirmed COVID-19. Conventional morphological and immunohistochemical methods were used. Results: There was an acute exudative hemorrhagic pneumonia with the formation of hyaline membranes, focal organization of fibrin, stromal sclerosis, stasis, and thrombus formation in the lung vessels. Signs such as the formation of hyaline membranes, organization, and fibrosis were more pronounced in severe disease activity. The activation of CD68+/CD163+ macrophages could cause cell damage at an early stage of pneumonia development, and subsequently cause fibrotic changes in lung tissue. ACE2 expression in lung tissue was not detected in severe pneumonia, while in moderate pneumonia, weak expression was noted in individual cells of the alveolar epithelium and vascular endothelium. Conclusions: This finding could show the dependence of ACE2 expression on the severity of the inflammatory process in the lungs. The expression of caspase-3 was more pronounced in severe pneumonia.

Background. Objectification of the choice of treatment methods based on a comprehensive assessment of their effectiveness depending on the stage of diabetic retinopathy (DR) and biomarkers characterizing the state of the eye, metabolism and other parameters of homeostasis is an urgent modern task of precision medicine. The purpose of the study was to establish the effectiveness of treatment methods in DR of various stages and to determine prognostic indicators of the risk of its rapid progression during 2 years of treatment in the setting of an ophthalmological hospital. Materials and me­thods. Three hundred and fifty-eight patients (358 eyes) with type 2 diabetes mellitus (T2DM) and DR were examined and divided into the following groups: first one — nonproliferative DR (NPDR, 189 eyes), second one — with preproliferative DR (PPDR; 96 eyes) and the third one — proliferative DR (PDR; 73 eyes). The patients were examined using ophthalmic methods: the central retinal thickness (CRT, μm) and the central retinal volume (CRV, mm3) were determined according to optical coherence tomography data. The analysis of the results was carried out in the EZR v. 1.54 package (Austria), the classification of models — in the Statistica Neural Networks v. 4.0C (StatSoft Inc.). The method of building linear neural network classification models was used to analyze the influence of factor characteristics associated with the risk of DR progression. Results. Rapid progression was noted in 16.9 % of patients with NPDR who received conservative treatment for 2 years, its risk was associated with the value of the CRV (p < 0.001). For conservative and laser treatment, the thresholds for a negative prognosis were found by the value of the CRV (more than 0.285 and 0.180 mm3, respectively). For anti-VEGF therapy and combined treatment, the prognosis of effectiveness was negative. Rapid progression of PPDR was detected in 69.5 % of patients. Its risk was associated with the type of treatment and the size of the CRT, according to which the thresholds of a negative prognosis were established for anti-VEGF therapy and combined treatment (more than 345 and 185 μm, respectively). The prognosis of the effectiveness of laser and surgical treatment in PPDR was positive. Rapid progression of PDR within 2 years was noted in 69.9 % of patients. Its risk was associated with the type of treatment, prothrombin time, and the value of the CRV, which determined the effectiveness of surgical and combined treatment. For anti-VEGF therapy alone, the prognosis of effectiveness was negative. Conclusions. The study conducted made it possible to evaluate the effectiveness of treatment methods in DR of various stages and to establish factors associated with a negative risk of the outcome of two-year treatment.

One of the primary mechanisms of retinal neurodegeneration in diabetes mellitus is gamma-aminobutyric acid (GABA) deficiency that makes the use of GABA-benzodiazepine receptor modulators a promising option for the correction of this diabetic complication. The aim of this study was to determine the effect of the benzodiazepine receptor agonist carbacetam on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in retina of rats with hyperglycemia. Experimental diabetes was modeled by a single administration of streptozotocin (50 mg/kg) to three-month-old male Wistar rats. Immunoblotting and immunohistochemical studies were performed using monoclonal antibodies against VEGF and HIF-1α. It was shown that the development of diabetic retinopathy (DR) at the early stages was accompanied by a progressive multifold increase in the retina content of VEGF on 7-28 days and HIF-1α on 28th day. Insulin and insulin+carbacetam treatment significantly alleviated diabetes-induced overexpression of both HIF-1α and VEGF. Carbacetam was shown to block the diabetogenic increase in VEGF content in retina. The introduction of insulin with carbacetam significantly reduced the expression of VEGF and the development of specific morphological manifestations of DR. Thus, restoration of GABA-ergic signaling can be used as a promising therapeutic option for the correction of DR disorders. Keywords: carbacetam, GABA-benzodia­zepine receptors, HIF-1α hyperglycemia, retinopathy, streptozotocin-induced diabetes, VEGF

The positive effect of cellular protein kinases blockade in diabetes and diabetic retinopathy (DR) justifies the need to clarify molecular mechanisms, among which the trigger regulatory role belongs to calcium-binding proteins S100. Aim: to establish the expression of S100 protein in retinal tissues and the effect of cellular protein kinases blockade with Sorafenib on it in experimental DR. Materials and methods. Diabetic retinopathy was modeled in male Wistar rats. For this purpose, they were administered a single injection of streptozotocin at a dose of 50 mg/kg (Sigma-Aldrich, Co, China). Experimental rats were divided into three groups: control; with the administration of insulin 30 U (NovoNordiskA/S, Bagsvaerd, Germany); with the administration of insulin and sorafenib at a dose of 50 mg/kg (Cipla, India). Monoclonal antibodies against S100 (ThermoFisher Scietific, USA) were used during immunohistochemical studies. Results. With the development of experimental DR, the expression of S100 protein significantly increased in the bodies and processes of astrocytes and Müller cells. The latter were mainly located in the inner nuclear layer, significantly increased in size and had a process-like shape (reactive gliosis). Intensely stained S100-positive astrocyte fibers were in close contact with microaneurysms that formed on the retina inner surface. The appearance of individual S100-positive cells in the outer layers of the retina was noted. Treatment of animals with insulin led to a decrease in the expression of the S100 protein, and the use of Sorafenib prevented the activation of the expression of the S100 protein, preventing the development of DR, reactive gliosis, and the formation of microaneurysms on the inner surface of the retina. Conclusions. One of the mechanisms of the positive effect of Sorafenib in DR was discovered – the prevention of reactive gliosis, which prevented early manifestations of DR.

In experimental heavy closed brain injury (mortality infive days - 86%) it is shown that from the first hours the violations of carbohydrate metabolism in the form of triad were formed: the marked hyperglycemia (3.3-3.6 times), hyperinsulinemia (2.4-3.2 times) and insulin resistance (HOMA-indexes increased to 8.0-11.7 times). These changes were caused by a decrease in tissue sensitivity to insulin and were accompanied by decrease in functional activity of the pancreatic β-cells. In total it is possible to consider these changes as a pentad of the typical disorders of carbohydrate metabolism at brain injury.

Зв’язок ендотеліну-1 з розвитком рецидивів при хірургічному лікуванні діабетичної макулопатії у хворих на цукровий діабет 2 типу