Skin microcirculation reactivity to local thermal hyperaemia in patients with COVID-19 - A pilot observational study.

BACKGROUND: Endothelial dysfunction and microvascular disturbances are suggested to play a key role in higher morbidity and worse prognosis in patients with COVID-19 and cardiometabolic diseases. OBJECTIVE: Study was aimed to establish relationships between the skin microcirculation parameters and various clinical and laboratory indicators. METHODS: The study included 18 patients with moderate disease according to WHO criteria. Skin microcirculation measurements were performed by laser Doppler flowmetry using a heating test on the hairy skin of the right forearm. RESULTS: Baseline perfusion only correlated with C-reactive protein (Rs = 0.5, p = 0.034). Microcirculation indices characterising the development of hyperaemia during the first minute of heating (LTH1 and AUC60) showed significant correlations (Rs from 0.48 to 0.67, p < 0.05) with indices of general blood analysis and blood coagulation (fibrinogen, D-dimer, haemoglobin, erythrocyte count and haematocrit). Indexes characterising the dynamics of hyperaemia development over longer time intervals showed correlation with the glomerular filtration rate (Rs = 0.6, p = 0.009). CONCLUSION: Known COVID-19 risk factors (haemorheological parameters, age) are correlated with the microvascular reactivity to heating in patients with COVID 19. We suggest that, prospectively, the method of laser Doppler flowmetry could be used for non-invasive instrumental assessment of microcirculatory disorders in patients with COVID-19.

[New approaches for recovery of erectile function in patients after radical prostatectomy].

Prostate cancer (PCa) is one of the most common maligmancies and causes of death among men. Radical prostatectomy (RP) is optimal and recommended treatment modality for localized prostate cancer. More than half of all men undergoing surgery experience problems with erectile function and existing treatments do not provide a positive effect. Thus, there is a need for new approaches to the restoration of erectile function in patients after RP. One of these is the use of cell technologies, namely the stromal-vascular fraction and autologous platelet-rich plasma. This review examines the results of preclinical and clinical studies investigating the efficacy and safety of these treatment options in erectile dysfunction.

[Significance of the determination of urinary excretion of kidney injury molecule-1 (KIM-1) in the assessment of the activity and prognosis of chronic glomerulonephritis].

AIM: To estimate the urinary excretion of KIM-1 in groups of patients with varying clinical activity of chronic glomerulonephritis (CGN) and to determine the possibility of using the urinary KIM-1 concentration as a criterion for predicting the course of CGN. SUBJECTS AND METHODS: A total of 47 patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased glomerular filtration rate (GFR); Group 2 consisted of 16 patients with NS and normal GFR; Group 3 comprised 10 patients with partial remission of NS; Group 4 included 11 patients with CGN, hematuria, moderate proteinuria, and normal GFR. A control group consisted of 9 healthy individuals. In the examined groups, urinary KIM-1 concentrations were estimated using an indirect immunoassay. RESULTS: The urinary KIM-1 excretion in the patients with CGN was higher than that in the healthy individuals (p <0.0001), at the same time, in the average the KIM-1 excretion was statistically significantly higher in the patients with proteinuria than in those with hematuria (p=0.01). The highest levels were registered in Group 1; Group 2 was intermediate in the level of KIM-1 excretion and the difference between Groups 3 and 4 proved to be statistically insignificant. The lowest levels were noted in Group 4 and in the controls; the differences between the groups were statistically insignificant. In the patients with CGN, the level of KIM-1 excretion was established to correlate with all indicators of NS severity. The value of the determination of KIM-1 as a risk factor of persistent/refractory NS was estimated. The results of constructing the ROC-curve indicate that KIM-1 levels higher than 2.34 ng/ml could predict NS persistence in CGN patients with a high sensitivity and specificity. CONCLUSION: Urinary KIM-1 levels may be used to estimate the activity of CGN with NS and to evaluate the efficiency of treatment. The results of the study substantiate the search for ways of pharmacological blockade of KIM-1 production in the kidney in order to optimize the methods that impact on the pathogenesis of CGN progression.

[Slow Formation and Degradation of γH2AX Foci in Human Skin Fibroblasts Exposed to Low-Dose X-Ray Radiation].

It was shown that the kinetics of changes of γH2AX foci number (marker of DNA double-strand breaks) in human skin fibroblasts after exposure to low doses of X-ray radiation (20, 40 and 80 mGy) differs from that observed after exposure to medium-low doses (160 and 240 mGy). After exposure to 160 and 240 mGy the highest number of γH2AX foci was detected at 30 min after exposure (first experimental point) and further their decrease was observed. At the same time we observed a fast phase of repair (upto 4 h), in which there was a decrease of the foci amount to ~50-60% and a slow phase of repair (from 4 h to 24 h). After 24 h only ~3-5% of the foci amount observed at 30 min after irradiation was left. After exposure to low doses, the foci number did not decrease during 2 h and even 24 h after exposure their amount was ~25% from that observed at maximum points (1 h after irradiation at 40 and 80 mGy and 2 h after irradiation at 20 mGy).

[Prospects for the use of cells possessing myogenic potential in the treatment of skeletal muscle diseases: a review of research. Part 1 - satellite cells].

Musculoskeletal functions disorders may develop as a consequence of injuries and various types of congenital / acquired diseases, among which a special place belongs to muscular dystrophy. The technology with use of cells possessing myogenic potential is considered as one of the most promising approaches to solve the problem of effective restoration of skeletal muscles structure and function. In part I of the article the characteristic features, functions and phenotypic characteristics of satellite cells (SC) are reviewed as key factors of skeletal muscle tissue regeneration. Presented analysis of research results (preclinical and clinical) concerning therapeutic possibilities of technology using SC. In the second part of review will be presented data of the therapeutic use of stem cells of muscle and non-muscle origin for the treatment of skeletal muscles diseases.

[Prospects for the Use of Cells Possessing Myogenic Potential in the Treatment of Skeletal Muscle Diseases: a Review of Research. Part 2--Populations of stem cells of muscle and non-muscle origin].

The paper reviews research results of myogenic potential, specific properties, functions, and phenotypic features of a number of stem cells populations of muscle and non-muscle origin, their ability to participate in the restoration of the physiological homeostasis of skeletal muscle. The results of scientific research allow to predict with high probability the establishment of an effective cell technology to treat degenerative muscle diseases.

[Clinical significance of serum and urinary biomarkers for water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis].

AIM: To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease. SUBJECTS AND METHODS: Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN. A control group consisted of 9 healthy individuals matched for gender and age with the patients with CGN. The serum level of copeptin and the urinary excretion of aquaporine-2 (AQP-2) and kidney injury molecule-1 (KIM-1) were determined by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: In the NS patients with and without renal dysfunction, the serum copeptin concentration was significantly higher than that in those with partial remission of NS or hematuric CGN and in the controls. In the patients with hematuric CGN, this indicator was virtually different from that in the control group. Urinary AQP-2 excretion was significantly similar in 3 NS groups. In the patients with hematuric CGN, the urinary AQP-2 concentration was higher than that in those with NS, but it was significantly lower than in the control group. The highest urinary excretion of KIM-1 was found in the patients with NS and diminished renal function while its excretion was significantly lower in the patients with NS and stable renal function, as in those with partial remission of NS. The lowest values were seen in the patients with hematuric CGN and in the control group; the differences between these groups were statistically insignificant. Correlation analysis showed that there was an inverse correlation between serum copeptin and urinary AQP-2 levels and between urinary AQP- 2 and KIM-1 levels. CONCLUSION: Serum copeptin levels and urinary AQP-2 secretion may be used to assess the activity of CGN and NS and to evaluate therapeutic effectiveness. The determination of urinary KIM-1 excretion may be of the same practical value in patients with NS. It has been shown that the concentrations of copeptin, APQ-2, and KIM-1 may be used as a differential diagnostic criterion for hematuric CGN.

[The significance of natriuretic peptides in the evaluation of water-salt metabolism in chronic kidney disease].

The paper discusses the molecular, biochemical, and physiological properties of natriuretic peptides, including the clinical applications of their synthetic formulations, as well as the renal and extrarenal mechanisms of water-salt metabolism in chronic kidney disease.

[Nephropathy in Fabry disease: possibilities for the radical improvement of prognosis for orphan diseases].

The paper discusses the specific features of the diagnosis and treatment of kidney involvement in patients with Fabry disease.

[Endothelial function in patients with arterial hypertension and impaired uric acid metabolism].

The aim of the study was to investigate endothelial function in patients with arterial hypertension and impaired uric acid metabolism in comparison with patients having arterial hypertension and normal uric acid metabolism. 46 patients aged 32-56 yr with grade I-II AH were included in the study. A group of 36 patients (27 male, 9 female) presented with AH and impaired uric acid metabolism (hyperuricemia), the control group included 10 patients with AH and unaffected uric acid metabolism. Inclusion criteria in the two groups were identical. Endothelial dysfunction was documented in all patients and confirmed by increased levels of serum endothelin-1 and microalbuminuria, qualitative and quantitative changes in the intima-media complex and its thickening. These changes were much more pronounced in patients with hyperuricemia It is concluded that impaired uric acid metabolism in patients with AH leads to rapid onset and progression of endothelial dysfunction. This fact should be taken into consideration by doctors practicing antihypertensive treatment and for the evaluation of cardiovascular risks.

Reparative osteogenesis during transplantation of mesenchymal stem cells.

Reparative osteogenesis was studied after xenotransplantation of suspension cell graft from human mesenchymal stem cells. A model of experimental damage to rat femoral diaphysis was developed. The state of animals was satisfactory and non-depressed in the early and late postoperation period. We revealed no local pathological reactions and complications. Administration of mesenchymal stem cells into the area of bone defect accelerated and improved regeneration. Unilateral transplantation of the cell graft stimulated regeneration in the contralateral limb due to acceleration of bone tissue maturation. On day 90 after treatment the bone regenerate was completely developed in the area of defect in animals of various groups. The newly formed bone tissue was well integrated into the bone organ.

Stimulation of reparative osteogenesis after xenotransplantation of human prenatal mesenchymal stem cells and chondroblasts.

Regeneration of the bone tissue after unilateral xenogeneic transplantation of a suspension of human mesenchymal cells and chondroblasts was studied in rats with experimental damage to both femurs. The state of animals was satisfactory and non-depressed in the early and late postoperation period. No local pathological reactions and complications were seen. Administration of mesenchymal stem cells and chondroblasts into the area of bone defect accelerated regeneration on days 10 and 30 (compared to the control group). Implantation of mesenchymal stem cells more significantly stimulated reparative osteogenesis compared to treatment with chondroblasts. This was mainly associated with increased ratio of mature lamellar bone tissue. Unilateral transplantation of the cell suspension stimulated regeneration in the contralateral limb due to accelerated maturation of the bone tissue. The bone tissue formed after transplantation of mesenchymal stem cells and chondroblasts was integrated into bone organ and underwent complete remodeling. Xenotransplantation of prenatal mesenchymal stem cells and chondroblasts without immunosuppression was not followed by the development of early and delayed complications or local reactions of graft rejection.