[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.

World's First Clinical Case of Gene-Activated Bone Substitute Application.

Treatment of patients with large bone defects is a complex clinical problem. We have initiated the first clinical study of a gene-activated bone substitute composed of the collagen-hydroxyapatite scaffold and plasmid DNA encoding vascular endothelial growth factor. The first patient with two nonunions of previously reconstructed mandible was enrolled into the study. Scar tissues were excised; bone defects (5-14 mm) between the mandibular fragments and nonvascularized rib-bone autograft were filled in with the gene-activated bone substitute. No adverse events were observed during 12 months of follow-up. In 3 months, the average density of newly formed tissues within the implantation zone was 402.21 ± 84.40 and 447.68 ± 106.75 HU in the frontal and distal regions, respectively, which correlated with the density of spongy bone. Complete distal bone defect repair with vestibular and lingual cortical plates formation was observed in 6 and 12 months after surgery; thereby the posterior nonunion was successfully eliminated. However, there was partial resorption of the proximal edge of the autograft entailed to relapse of the anterior nonunion. Thus, the first clinical data on the safety and efficacy of the gene-activated bone substitute were obtained. Given a high complexity of the clinical situation the treatment, results might be considered as promising. NCT02293031.

[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.

[Characteristics of immune response and inflammatory reaction in atherothrombotic stroke and myocardial infarction]. / Osobennosti immunnogo otveta i vospalitel'noi reaktsii pri aterotromboticheskom insul'te i infarkte miokarda.

AIM: To study characteristics of ischemic tissue damage basing on the assessment of the correlations between markers of immune response, inflammation and apoptosis in patients with myocardial infarction (MI) and atherothrombotic stroke (AS). MATERIAL AND METHODS: Concentrations of matrix metalloproteinase-9 (MMP-9), immune complexes with cryogenic properties, soluble Fas-ligand, tumor necrosis factor alpha, interleukin-10 measured with ELISA as well as the activity of spontaneous apoptosis of mononuclear cells and surface expression of Toll-like receptors-4 and intracellular heat shock proteins measured with flow cytofluorometry were determined in the blood of 93 patients with the first AS and 94 patients with MI without concomitant inflammation in the 1st and 7th day of the disease. RESULTS AND CONCLUSION: Increased levels of the markers of immune response, inflammation, apoptosis and destruction of the extracellular matrix were identified at the beginning of MI and AS. The results provide the evidence that similar mechanisms may be involved in ischemic tissue damage. Multivariate analysis conducterd by of principal component analysis correlation matrix revealed the specificity of the relationships between all of these markers. This is the completely new approach to assessin the role and importance of defined parameters in the acute period of the myocardial ischemia and brain.

[Experimental model of severe local radiation injuries of the skin after X-rays].

The experimental model of severe local radiation injuries skin under the influence of a relatively soft X-rays on a modified device RAP 100-10 produced by "Diagnostica-M" (Russia) was proposed. The model can be used as pre-clinical studies in small experimental animals in order to improve the treatment of local radiation injuries, especially in the conditions of application of cellular therapy.

[Experience of contemporary treatment of radiation burns in individuals subjected to ionizing radiation].

The article presents new approach to treatment of radiation disorders presenting as indolent ulcers. The approach is based on autologous multipotent mesenchimal stromal cells applied locally and injected around the injuried zone. The ulcers heal due to the fact that the transplanted cells stimulate local regeneration processes, angiogenesis, ceased inflammation and apoptosis. The method is a new medical technology based on vast preclinical studies and could be put into medical practice.

[Mesenchymal stem cells transplantation in the treatment of radiation skin lesions].

Transplantation of mesenchymal stem cells, both at early and later stage after local exposure of rats source beta radiation dose, 90Sr/90Y 140 GR, stimulates recovery of damaged skin. Diminution area local radiation injuries and accelerate healing radiation ulcers. Clinically shows the high efficiency of the transplantations autologous mesenchymal stem cells in treatment of deep beam ulcers, intractable standard conservative treatment. Found promising application of mesenchymal stem cells for treatment of severe local radiation injuries and the need to develop the best possible conditions for their use.

[Stem cells technologies in the treatment of burns].

Effective treatment of bums is one of effective in present medicine. Using cellular technology is one of the perspective directions for restoration of the integrity of the skin after burn injury an overview of the commercial preparations, presented at the European and American markets, and technologies developed by leading institutions in Russia.

[Cryoglobulins in patients with ischemic stroke].

The composition of circulating immune complexes with cryo-properties (cryo-IC) were determined in 70 patients on days 1, 2, 3, 7, 14 and 21 after ischemic carotid stroke. The quantitative and qualitative assessments of cryo-IC content were conducted on a spectrophotometer and on a vertical electrophoresis, respectively. Concentrations of immunoglobulins (Ig) M, A and C, fibronectin, percentage of IgM with rheumatoid factor activity, IgG isotypes (IgG1, IgG2, IgG3, IgG4) were measured with ELISA. The control group included 15 healthy age- and sex-matched people. Compared to the controls, the cryo-IC content was higher in 100% of patients studied, it was higher in atherothrombotic variant than in cardioembolic one. The cryo-IC level was directly correlated with the clinical state severity (p < 0.01). IgG, IgM and fibronectin were observed in 100%, IgA--in 11% and IgM with rheumatoid factor activity--in 6% of patients. The percentage of IgG1 and IgG2 was not less than 90% of the total amount, with the IgG1 percentage about 50%. Cryo-IC changing in the time in dependence on ischemic variant were formed on different stages of development of acute brain ischemia. Dependence of concentrations of fibronectin and IgG, IgA, IgM on the time of observation was similar for both variants of ischemic stroke, but with a time axis shift, running faster and with a smaller range of changes of parameters studied in cardioembolic than in atherothrombotic stroke.

[Dynamics of blood fibronectin and its correlation with the phenomenon of cryoglobulinemia in patients with ischemic stroke].

Seventy patients with carotid ischemic stroke (38 with atherothrombotic and 32 with cardioembolic variants) were examined. The dynamics of fibronectin level and its correlation with blood cryoglobulins concentrations were evaluated in the 1st, 2nd, 3rd, 7th, 14th and 21st days after disease onset. The quantitative assessment of cryoglobulins content was carried out using spectrophotometric method; fibronectin concentration was measured by ELISA. In patients with atherothrombotic variant of stroke, the level of fibronectin in the blood serum and in the cryocomplex was higher compared to patients with cardioembolic variant in the 1st day (p < 0.001) and during all the period of the study (p < 0.05). The concentration of cryocomplexes in the blood serum of patients with ischemic stroke was in reverse correlation with percentage of fibronectin in their content and with the pathogenetic variant of ischemia (r = -0.94; p < 0.05 and r = -0.87; p < 0.05 or atherothrombotic and cardioembolic variants, respectively).

[An effect of perindopril on the level of tumor necrosis factor-alpha and matrix metalloproteinase-9 in peripheral blood in the acute period of atherothrombotic ischemic stroke and myocardial infarction].

Twenty-nine patients with acute atherothrombotic ischemic stroke and 36 patients with acute Q-wave myocardial infarction have been studied. Each group has been stratified into 2 subgroups: patients of subgroups A received an ACE inhibitor perindopril in the complex therapy from the 1st day of disease. Patients of subgroups B were not assigned to this drug. Along with routine tests, the level of tumor necrosis factor-alpha and matrix metalloproteinase-9 (MMP-9) measured with ELISA using test-systems (BCM Diagnostics, USA) and reagents (R&D, England) have been determined. The administration of perindopril did not cause side-effects, including arterial hypotonia after the first dosage, in patients in the acute period of atherothrombotic ischemic stroke and myocardial infarction. Perindopril may decrease the activity of MMP-9 in these patients and produces an anticytokine effect. Some similar mechanisms of ischemic lesions of the heart and the brain and a commonness of biochemical "response" to the same medical intervention (the administration of an ACE inhibitor perindopril) in patients of both groups were found. The results support the pathogenetic validity of perindopril therapy in the secondary prevention of ischemic stroke and myocardial infarction.

The use of statistical methods for predicting the status of patients with acute cerebral and coronary ischemia.

The most significant informative clinical laboratory parameters were determined and the exceptional value of cryoglobulin concentrations for predicting the clinical status was demonstrated. The efficiency of the proposed protocol of selective plasmapheresis for patients with atherothrombotic variant of stroke is confirmed, mathematical models describing and predicting the patient status are plotted.

Cryoglobulin level in patients with ischemic stroke and effect of selective plasmapheresis on this parameter.

Serum concentrations of cryoglobulins were measured in patients with ischemic stroke; inadequate changes in these concentrations over the course of the entire acute period of the disease were shown. Positive effect of selective plasmapheresis on the decrease in cryoglobulin concentration and recovery of patients was confirmed.

[Crioglobulinemia in cerebral and coronal atherothrombosis].

Forty-seven patients: group A--17 patients with acute ischemic atherothrombotic stroke and group B--30 patients with acute Q-formation myocardial infarction. The levels of dynamics and comparative clinical relevance of crioglobulinemia in patients of the both groups have been evaluated. Crioglobulines (CG) in the peripheral blood serum were determined at 1, 2, 3, 7th and 14th days after the disease development. On the 1st day, the elevated CG level similar in the both groups as well as similarity of crioglobulinemia dynamics in whole was observed. In the group A, but not in the group B, the CG level was directly correlated with disease severity (p<0,05). In the group B, there was a trend, which depended on the blood CG level on the 1st day of the disease and on the presence of previous stenocardia (p<0,1).

[Cryoglobulinemia and extracorporal plasma therapy in severe ischemic stroke]. / Krioglobulinemiia i ee korrektsiia pri ostrom ishemicheskom insul'te.

Forty-five patients with carotid ischemic stroke have been examined within the first 24 hours from the disease onset. The Orgogozo and NIH scales were used to objectify a severity of the patient's state and the Barthel scale--to evaluate a degree of functional rehabilitation. Cryoglobulins (CG) were measured in blood serum by spectrophotometric method on the 1st, 2nd, 3rd, 7th and 21st days. Selective plasmapheresis was included in the therapeutic complex for 22 randomly selected patients. In both groups, a level of CG positively correlated with a severity of the patient's state on the 1st day of the monitoring (r=-0.5; p<0.01). The study of hemostasis indicated the presence of a direct correlation between an increase of platelet aggregation, blood hyperviscosity and CG concentration (r=0.46; p<0.05 and r=0.74; p<0.01, respectively). Higher scoring on the Orgogozo scale and Barthel scale prevailed in the group treated with plasmapheresis that significantly correlated with a decrease in CG concentration in blood serum (r=-0.6; p<0.05 and r=0.5; p<0.05 respectively). An evaluation of platelet aggregation, blood viscosity and a coagulogram on the 21st day of the disease revealed a significant improvement of blood rheology in the group of patients switched to efferent therapy.