Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

[Effectiveness of physical rehabilitation methods based on the impact of eccentric load in upper limb injuries]. / Effektivnost' fizicheskikh metodov reabilitatsii, osnovannykh na vozdeistvii ekstsentricheskikh nagruzok, pri travmakh verkhnikh konechnostei.

The rehabilitation of patients after upper limb injuries is becoming increasingly relevant in current medical practice considering that this pathology is often occurred in professional athletes, elderly people, people with active lifestyle. OBJECTIVE: To study the effectiveness of isolated therapeutic exercises (TE) with eccentric muscle loads when using rubber cable compared to traditional TE to restore functional capabilities of patients after upper limb injuries. MATERIAL AND METHODS: The study included 38 patients with upper limb injuries diagnosed by orthopedic surgeon. Patients were randomly enrolled into group of isolated TE with eccentric muscle loads (group A, 20 patients, mean age 40.2±10.8 years) and group of traditional exercises (group B, 18 patients, mean age 38.6±12.3 years). The study consisted of anamnesis taking, clinical examination, functional tests applying (isometric dynamometry, joint mobility tests, functional scales and questionnaires). The rehabilitation effectiveness was assessed by comparing the indicators before and after treatment course. RESULTS: There has been a significant improvement in muscle strength, movement amplitude and decrease of pain syndrome in patients rehabilitated by eccentric muscle loads. A comparison with a control group using traditional TE methods confirmed the superiority of eccentric exercises in reducing recovery time and improving functional performance. CONCLUSION: The study confirmed the high effectiveness of eccentric muscular loads in the rehabilitation of patients after upper limb injuries. The method has shown significant improvement in clinical and functional indices, which allows to recommend it for inclusion in standard rehabilitation protocols. Further researches may extend application of this approach and reveal the TE effectiveness in other types of traumas and orthopedic injuries.

[Physical methods of correction of arterial hypertension: modern concepts. (A literature review)]. / Fizicheskie metody korrektsii arterial'noi gipertenzii: sovremennye predstavleniya. (Obzor literatury).

Arterial hypertension is a major risk factor for cardiovascular disease, affecting a large proportion of the population worldwide. The study of the listed literature made it possible to assess the effectiveness and necessity of physical exercise in the treatment of hypertension syndrome, including various types of exercise, intensity, duration, and frequency, since drug treatment is not enough for successful therapy. To prevent and treat hypertension, a comprehensive approach is required, including aerobic exercise, which will lower blood pressure by dilating blood vessels.

[Efficacy of manual correction of cervical spine osteochondrosis in the treatment of arterial hypertension syndrome and prediabetes]. / Effektivnost' manual'noi korrektsii osteokhondroza sheinogo otdela pozvonochnika v terapii sindroma arterial'noi gipertenzii i prediabeta.

Cardiovascular diseases and diabetes mellitus, debuting as arterial hypertension (AH) syndrome and prediabetes, are common types of chronic non-communicable processes, that are the leading cause of death in the world. The main treatment method for above mentioned disorders, according to the current guidelines, is pharmacotherapy. However, it is possible to effectively apply non-pharmacological correction methods, aimed at the probable etiological factor and inversive mechanism involved in AH maintenance, in the early stages when no permanent changes are maintaining a high level of blood hypertension (BH) and glycemia. Frequently, this mechanism is hypoxia in the vertebral arteries system due to cervical spine osteochondrosis. OBJECTIVE: To evaluate the therapeutic effect of non-pharmacological methods of restoring brainstem blood supply in patients with AH and prediabetes. MATERIAL AND METHODS: The number of patients equal 125 (57 men and 68 women, mean age 63.3±11.5 and 65.4±11.8 y.o., respectively) with prediabetes and 1st degree of AH without target organs damage, among whom 102 patients with prehypertension or 1st degree of hypertension and 24 ones with 2nd degree of hypertension, were examined. The original method of manually restoring brainstem blood supply developed in the Shishonin's Clinic was applied to all patients. The control group included patients with the same disorder, who did not receive manipulations. Blood pressure (BP) measurement, ultrasound and triplex ultrasonography of vertebral arteries, biochemical blood test, and estimation of glycemia and glycated hemoglobin were performed. RESULTS: All patients of the study group had decreased levels of systolic BP (by 23.8±10.7 mm Hg for men and 32.8±11.9 mm Hg for women), an increase of flow velocity in vertebral arteries (by 20.6±7.5 and 21.5±7.2 cm/s, respectively), a decrease of glycated hemoglobin concentration (by 0.32±0.51 and 0.34±0.41%, respectively). In the comparison group, there were no patients with improvement in these indicators. CONCLUSION: The effectiveness of the author's manual method of cervical spine osteochondrosis correction in the reduction of BP and glycemia levels in the early stages of the disease is shown.

[Theory of centralized aerobic-anaerobic energy balance compensation and non-pharmaceutical treatment methods of arterial hypertension]. / Teoriya tsentralizovannoi kompensatsii aerobno-anaerobnogo energeticheskogo balansa i nelekarstvennye metody lecheniya arterial'noi gipertenzii.

Several chronic non-communicable diseases are associated with arterial hypertension and are closely related to increased blood pressure. The theory of centralized aerobic-anaerobic energy balance compensation (TCAAEBC) was formulated in connection with the above-mentioned processes. This theory, including the hypothesis of the «egoistic brain¼, is a broader concept. The key point of TCAAEBC is hypoxic anaerobic metabolism, which affects reflex vascular zones, including the neurons of the respiratory and cardiovascular centers of the rhomboid fossa of the medulla oblongata. Hypoxia correction using manual techniques, physical exercises, and other non-pharmaceutical methods under certain conditions can stabilize the level of blood pressure and has a curative effect in the case of arterial hypertension syndrome.

Characterization of Risk Factors for Modeling of Type 2 Diabetes Mellitus Induced by a High-Fat Diet in C57BL/6 Mice.

Type 2 diabetes mellitus develops due to a combination of genetic and environmental factors. C57BL/6 mice prone to obesity and leptin resistance were kept on a high-fat diet for 21 weeks. The animals showed a significant increase in fasting and postprandial glucose levels and body weight, the development of insulin resistance, and by week 18, an increase in the serum TNFα level. Metformin therapy at a dose of 250 mg/kg was effective against the background of disturbances in carbohydrate metabolism: animals showed a significant decrease in insulin resistance and TNFα level.

[Predictors of therapeutic efficacy of immune response checkpoint inhibitors in clear cell renal cell carcinoma].

Immunotherapy in oncologic diseases involves the use of drugs which stimulate the immune system and indirectly suppress tumor cells growth. These agents have expanded the treatment options for cancer patients. Despite the impressive success achieved in the development of immune checkpoint inhibitors (ICIs) and subsequent approval in a broader spectrum of malignant tumors, most patients are not responded the therapy. Currently available predictive markers of efficacy are nonspecific. However, microRNAs are of particular interest, which regulate gene expression and are involved in the carcinogenesis and therapy resistance. Therefore, it is clear that for the most efficient and cost-effective use of ICIs, it is important to have validated biomarkers that will accurately predict the therapeutic response. The published results on molecular genetic changes in patients with renal cell carcinoma (RCC) were analyzed and summarized in order to determine possible prognostic biomarkers when prescribing ICI therapy.

[Regnerative technologies in reconstructive operations on the urethra: a review. Part 2].

Recent advances in the treatment of urethral strictures are associated with regenerative medicine and tissue engineering. Urethral reconstruction in some cases is a difficult task for urologists due to the insufficient amount of autologous tissue and relapses, which encourages clinicians to search for alternatives. The purpose of this work is to review the latest achievements in the use of regenerative technologies, biomaterials and cell therapy in urethroplasty. The second part of the literature review presents the prospects of using the stromal vascular fraction (SVF) of autologous adipose tissue during reconstructive operations on the urethra, especially considering the availability of these cells through lipoaspiration. Tissue engineering technologies are reflected, which offer their own solutions to problems and limitations of their use. The article also provides examples of experimental studies in which cell-free and cellular biomaterials were used for urethral reconstruction. We believe that the approach of using SVF and biomatrix can become a potentially safe and effective method of therapy associated with the acceleration of regeneration processes, and can be of great benefit to patients with urethral diseases in the future.

[Investigation of the role of polymorphic loci RS2299941, RS1903858, RS10490920, RS2735343 of the PTEN gene in patients with prostate cancer].

Prostate cancer is a clinically heterogeneous disease, and accurate risk stratification of patients is becoming a key clinical task. This is the most common malignant neoplasm and the leading cause of cancer death in men worldwide. Genomic markers include tools and technologies that can predict the probability of an initial positive biopsy, reduce the number of unnecessary repeated biopsies, identify tumors with low, medium and high risk, classify the degree of disease, as well as predict and monitor the clinical response to intervention. Variants of the PTEN gene are of great interest as genetic markers of the risk of developing prostate malignancies.

[Beta-blockers for reducing intraoperative bleeding during rhinosinusosurgical operations in elderly and senile patients.]

With the ineffectiveness of conservative therapy of chronic rhinosinusitis in all age groups of patients, functional rhinosinusosurgical endoscopic interventions are now often used to do. The minimal bleeding is a necessary condition for their realization. There are reports of the use of beta-blockers for reducing surgical bleeding, but the possibility of their intravenous use in older patients has not been sufficiently studied. The aim of the work was to evaluate the effectiveness of intravenous metoprolol to reduce the bleeding intensity (BI) during rhinosinusosurgical interventions under general anesthesia in elderly and senile patients. The BI was assessed on the Fromme-Boezaart Score scale at different stages of the operation from the 10th to the 60th minute in two groups of patients: without (WM) and using metoprolol (M). It was shown that at the 30th minute of the operation BI was significantly lower in M group. Multivariate analysis of hemodynamic parameters demonstrated a direct relationship between heart rate (HR) and the development of bleeding. In the WM group, the probability of significant bleeding was 8,6 times higher. It has been shown that intraoperative intravenous use of metoprolol reduces the intensity of local bleeding during endoscopic rhinosinusosurgical operations.

[Physiotherapeutic methods in ophthalmic rehabilitation of patients with glaucoma and cataract]. / Fizioterapevticheskie metody v oftal'moreabilitatsii patsientov s sochetannoi glaukomoi i kataraktoi.

The authors analyzed scientific data on physiotherapeutic measures in the treatment of combined glaucoma and cataracts as one of the main causes of blindness and low vision.

Exosomal miRNA-146a is downregulated in clear cell renal cell carcinoma patients with severe immune-related adverse events.

Here we report the results of the pilot project of exosomal miRNA expression levels in clear cell renal cell carcinoma (ccRCC) patients with different clinical response to ICIs (nivolumab) and treatment related toxicity. Immune-related adverse events (irAEs) are a major cause of immune checkpoint inhibitors cancellation and therapy failure. Modern studies demonstrate evidence that exosomes are of great importance in the formation of tumor resistance to ICIs drugs and therapy. We performed exosomal miRNA-146a expression analysis using qPCR on 86 ccRCC patients and revealed a statistically significant (p = 0.01) decreased expression level in ccRCC patients with CTCAE grade 3-4 (M±SEM 1.71 ± 0.13) compared to CTCAE grade 0-2 group (M±SEM 2.30 ± 0.24). The expression levels of miRNA-126, miRNA-218 and miRNA-410 did not show statistically significant differences in the comparison groups (p > 0.05). Association analysis of rs2910164 in the miRNA-146a gene demonstrated that CC genotype and C allele carriers had higher risk of developing severe irAEs (p = 0.03, OR = 6.12; p = 0.01, OR = 2.42, respectively) compare with GG and GC carriers. That is the first attempt to identify biomarkers of ICIs treatment efficacy for ccRCC in the Volga-Ural region based on exosomal miRNAs analysis.

Antithrombotic Activity of the Antiplatelet Agent Angipur on the Model of Arterial Thrombosis in Rats with Isoproterenol-Induced Myocardial Infarction.

We studied the effect of Angipur on the process of experimental thrombosis induced by damage to the carotid artery wall by surface application of 50% ferric chloride (III) solution in rats without comorbidities and with isoproterenol-induced myocardial infarction. In animals without comorbidities, Angipur administered intravenously was 1.2 times less effective, in terms of ED50, than the well-known inhibitor of GPIIb/IIIa platelet receptors tirofiban. However, under conditions of non-coronary myocardial infarction, Angipur significantly prolonged the time of thrombus formation and exhibited 1.4-fold higher activity than the reference drug tirofiban.

[Clinical case of mucormycosis in patient COVID-19. Case report].

The COVID-19 epidemic is being revealed from a new angle every month. In particular, with the appearance of the delta strain, mucormycosis began to manifest in some patients, which had previously been extremely rare. Mucormycosis is a rare, aggressive infection caused by filamentous fungi of the Mucorales family and associated with high morbidity and mortality rates. The main risk factors for the mucormycosis in patients with COVID-19 are diabetes mellitus and diabetic ketoacidosis, uncontrolled hyperglycemia and massive use of glucocorticoids, vascular damage, thrombosis, lymphopenia, which often occur against the background of COVID-19 and make a person vulnerable to secondary or opportunistic fungal infection. We present a clinical case of mucormycosis in a 21-year-old female patient with COVID-19-associated severe pneumonia and concomitant type I diabetes mellitus. The patient was hospitalized and received standard therapy during inpatient treatment, including glucocorticosteroids in accordance with the severity of the course of COVID-19. On the 12th day from the hospitalization, the patient's condition deteriorated significantly, and the visible changes in the skin and soft tissues of the face, characteristic of mucormycosis appeared. Despite the drug therapy correction, the patient died because of the acute respiratory failure in combination with septic fungal damage of the brain stem.

[The use of prostate extract preparations in patients after transurethral resection of prostate for its benign hyperplasia].

The purpose of the study is to study the efficacy and safety of the prostate extract (GEROFARM LLC, Russia) in the postoperative period in patients after transurethral bipolar resection of the prostate. MATERIALS AND METHODS: The clinical study included 127 men aged 50 to 78 years with grade II benign prostatic hyperplasia (adenoma) who underwent a typical bipolar transurethral resection of the prostate. Patients of the main (n=60) group received tamsulosin 0.4 mg/day for 30 days in the postoperative period in combination with prostate extract 10 mg rectally for 21 days. In the control group (n=67) - tamsulosin 0.4 mg/day for 30 days as monotherapy. To assess the results of treatment, the questionnaire of the international system of total assessment of symptoms in prostate diseases (IPSS) with the definition of quality of life (QoL), the international index of erectile function (IIEF-5) and uroflowmetry were used. The control was carried out in terms of 1 and 3 months after the operation. RESULTS: In the main group, in the observation period of 1 and 3 months after the operation, a decrease in the average IPSS score by 40.2% and 52.9% was revealed, and an improvement in the quality of life by 45% and 64.7%, respectively, was noted. In the control group, at the same time of observation, a decrease in the average IPSS score by 34% and 44.7%, respectively, was revealed, and the quality of life improved by 25.5% and 37.3%, respectively. The increase in the average rate of urination in the main group by the end of 1 and 3 months of treatment was 59.2% and 85.7%, respectively, and in the control group, these figures were 40.5% and 50%. The positive effect of the proposed combination therapy on erectile function in the main group by the end of 1 and 3 months of treatment was 5.2% and 9.2%, respectively, and in the control group, these figures were 2.9% and 5.2%. DISCUSSION: There is a significant decrease in the symptoms of the lower urinary tract in the group of patients who received the drug Prostateks (GEROFARM LLC, Russia). CONCLUSIONS: The efficacy results of Prostatex (GEROFARM LLC, Russia) (reduced symptom severity on IPSS (11.7 1.2 ) and QoL (2.3 0.3)) scales are comparable to those of Vitprost Plus which allows you to evaluate the effectiveness of two drugs equally.

[Determination of cobalt in plasma blood samples by the ICP-MS method after oral intake of dietary supplements containing low doses of cobalt].

Salts of inorganic cobalt (Со) prevent the degradation of the alpha subunit of the hypoxia-inducible factor (HIF), imitating the state of hypoxia in the body and increasing the production of the endogenous hormone erythropoietin (EPO), and are used as doping substances that increase blood oxygen capacity and endurance, which give competitive advantages in sports. Currently, a large number of dietary supplements, including Co-containing ones, are offered on free sale. Their uncontrolled intake can affect not only the professional career of athletes, but also their health, due to the fact that this trace element and its salts are the strongest inorganic poisons and carcinogens. Despite this, their availability on the pharmaceutical market, a noticeable effect of erythropoiesis stimulation and a convenient oral form of administration lead to the need for their detection in modern doping control. The purpose of this research was to develop an approach to differentiate cobalt from vitamin B12, present in the body in its natural state, from the intake of cobalt salts by quantifying and comparing blood levels of vitamin B12 and total cobalt. Methods. The study involved 9 healthy volunteers (women and men) aged 25 to 45 years, leading an active lifestyle. Three of them took 2500 µg/day of cobalamin for 20 days (comparison group), three - dietary supplement containing cobalt asparaginate (100 µg/day in terms of pure cobalt), and the rest - dietary supplements with cobalt sulfate heptahydrate (100 µg/day in terms of pure cobalt) (administration groups) at the same time after meals. Blood samples were taken at baseline and on days 5, 9, 14 and 20. The concentrations of total cobalt in blood plasma samples of volunteers were measured by inductively coupled plasma mass-spectrometry (ICP-MS), the levels of cobalamin were determined on a Cobas 6000 immunochemical analyzer using the Elecsys Vitamin B12 II Assay ELISA kits. Results. It was found that oral intake of of cobalamin at a therapeutic dose significantly exceeding the recommended daily intake (3 µg), there was a regular slight increase in the blood concentration of total cobalt (1.1 times). At the same time intake of dietary supplements containing cobalt in the form of sulfate or asparaginate (about 100 µg per day in terms of pure cobalt) was accompanied by 4-6.7 fold increase in the concentration of total cobalt while unchanged vitamin B12 plasma concentration was observed. The detection of such changes can reliably indicate the use of prohibited salts and, of course, will be in demand for anti-doping control. Conclusion. Long-term monitoring of vitamin B12 and total cobalt levels, similar to hematological module of the Athlete Biological Passport program, will unambiguously detect possible abuse of cobalt salts and can be an additional evidence of the presence of these doping substances to other analytical methods, such as a combination of liquid chromatography and ICP-MS (LC-ICP-MS).

Experimental Study of the Efficacy of Sodium Deoxyribonucleate Used in Combination with Co-Transplantation of Mesenchymal and Hematopoietic Stem Cells after Exposure to γ-Radiation.

We studied the possibility of using sodium deoxyribonucleate (Derinat) for improving the efficiency of co-transplantation of mesenchymal (MSC) and hematopoietic stem cells (HSC) to female F1(CBA×C57BL/6) mice with bone marrow aplasia caused by exposure to γ-radiation. It was found that immunomodulator Derinat enhanced the effect of co-transplantation, in particular, triple post-irradiation administration of Derinat accelerated hematopoiesis recovery judging from the parameters of peripheral blood, total cellularity of the bone marrow and spleen, and animal survival. Single or double administration of Derinat prior to irradiation was ineffective. The optimal result was obtained when the following scheme was applied: MSC→HSC with an interval of 48 h starting during the first hours after irradiation and triple administration of Derinat (in 10-15 min, 3 and 7 days after irradiation) in a dose of 3 mg/mouse.

[A place of robot-assisted cystectomy in treatment of muscle-invasive bladder cancer].

Bladder cancer occupies one of the leading positions in morbidity in the world and constitutes a serious problem for healthcare system. The muscle-invasive bladder cancer is the most aggressive and more difficult to treat with drug therapy. Radical cystectomy is the standard treatment for muscle-invasive bladder cancer, with the most commonly used open approach. Currently, there is an active introduction of minimally invasive procedures, which is due to their advantages in perioperative care. Laparoscopic procedures have been broadly adopted for the oncourological practice, but the real breakthrough in the field of minimally invasive surgery has occurred after implementing of robotic-assisted interventions. It should be noted that the extensive radical procedures are associated with significant intra- and postoperative complications, which directly affects the patients condition and quality of life postoperatively. In this regard, robotic-assisted radical cystectomy appears to be a promising treatment method for muscle-invasive bladder cancer. The aim of this review is to collect and analyze current information on the results of robotic-assisted radical cystectomy, with particular attention to the comparison with open and laparoscopic techniques for different surgical and oncological outcomes.

[Airway support for endoscopic endonasal surgery in gerontology.]

Airway patency during ENT surgery in general anesthesia is a serious problem. It is important to manage the degree of intraoperative bleeding to improve the visibility of the surgical site and reduce the risk of complications. Airway management may affect the severity of intraoperative bleeding. We have shown that the use of a laryngeal mask during endoscopic endonasal rhinosinus surgery during general anesthesia reduces the severity of the hemodynamic response, which is expressed in an increase in heart rate, mean arterial pressure and intraoperative bleeding, and also reduces the risk of surgery.

Methylation and expression levels of microRNA-23b/-24-1/-27b, microRNA-30c-1/-30e, microRNA-301a and let-7g are dysregulated in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma is the most common form of kidney cancer in adults. DNA methylation of regulatory sequences at the genomic level and interaction between microRNAs and the messenger RNAs of target genes at the posttranscriptional level contribute to the dynamic regulation of gene activity. Aberrations in these mechanisms can result in impaired functioning of cell signaling pathways, such as that observed in malignant tumors. We hypothesized that microRNA genes methylation may be associated with renal cancer in patients. METHODS AND RESULTS: We examined methylation levels of 22 microRNA genes in tumor and normal kidney tissue of 30 patients with TNM Stage III clear cell renal cell carcinoma using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II PCR Arrays, Qiagen). MicroRNA expression analysis by quantitative polymerase chain reaction was also performed. Significant differences in methylation levels were found in two genes and in two clusters of microRNA genes. MicroRNA-23b/-24-1/-27b, microRNA -30c-1/-30e and let-7 g was hypermetylated in clear cell renal cell carcinoma tissue, microRNA -301a was hypomethylated in tumor compared with the adjacent normal tissues. Expression of microRNA-301a, microRNA-23b in the clear cell renal cell carcinoma tissues was significantly overexpressed when compared with the adjacent normal tissues and let-7 g was significantly downregulated in tumor. CONCLUSIONS: Our results may indicate the contribution of microRNA-301a, microRNA-23b and let-7 g in the pathogenesis of renal cancer, but further studies are needed to determine the functional significance of the detected changes.