[Influence of standard treatment on changes in the structural and functional properties of circulation red blood cells in obstructive and non-obstructive acute pyelonephritis].

AIM: To determine the effect of standard treatment on changes in the structural and functional properties of erythrocytes in obstructive and non-obstructive acute pyelonephritis. MATERIALS AND METHODS: The structural and functional properties of erythrocytes and their intracellular metabolism in 78 patients with a diagnosis of primary non-obstructive and secondary obstructive acute pyelonephritis, randomized by age, gender, and the minimum number of concomitant diseases were investigated. RESULTS AND DISCUSSION: In acute non-obstructive pyelonephritis, changes of the content of proteins in circulating erythrocytes responsible for the structure formation and stabilization of the plasma membrane (-spectrin, anion transport protein, pallidin, protein 4.1), intracellular metabolism (anion transport protein, glutathione-S-transferase), membrane flexibility and shape (actin, tropomyosin) are insignificant, alike from acute obstructive pyelonephritis. In addition, processes of lipid peroxidation inside red blood cells are intensified, and oxidative stress develops with a decrease in the sorption capacity of erythrocytes, as well as the content and ratio of lipid fractions in the plasma membrane, which form the basis of the lipid components and play the main role in the sequencing of protein macromolecules and the normal metabolism of red blood cells. CONCLUSION: In acute obstructive pyelonephritis, changes in the content and ratio of proteins and lipids in the erythrocyte membrane lead to functional rearrangements that are not corrected by standard treatment.

[Study of allelic variants of the CYP2D6 and CYP3A genes on the effectiveness and safety of tamsulosin therapy in patients with BPH: results of a pilot study].

INTRODUCTION: Tamsulosin is a member of the group of selective 1-adrenoblockers. Tamsulosin monotherapy is the most common first-line option in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and can be used regardless on severity of LUTS. The CYP2D6, CYP3A4, and CYP3A5 enzymes are involved in the metabolism of tamsulosin. Carriage of different allelic variants of CYP2D6, CYP3A4 and CYP3A5, involved in its metabolism, may potentially affect the variability of efficacy and safety of the drug. AIM: To evaluate the effect of carriage of allelic variants of cytochrome P450 superfamily enzyme genes (CYP2D6*3, CYP2D6*4, CYP2D6*9, CYP2D6*10, CYP2D6*41, CYP3A4*3, CYP3A4*22 and CYP3A5*3) on the efficiency and safety of tamsulosin in patients with LUTS associated with BPH. MATERIALS AND METHODS: All phases of the study were completed by 106 patients with LUTS/BPH (N40 according to ICD 10). All patients received monotherapy with tamsulosin 0.4 mg/day for a minimum of 8 weeks. Based on the severity of symptoms, they were divided into two groups using the International Prostate Symptom Score (IPSS). In Group 1, there were patients with moderate symptoms (IPSS score of 8-19) (n=57), while Group 2 consisted of those with severe symptoms (IPSS score >20) (n=49). Treatment outcomes were assessed using the IPSS score with determination of quality of life (QoL), transrectal ultrasound with evaluation of prostate volume and residual urine, and uroflowmetry. Follow-up visits were at 2, 4, and 8 weeks after the start of therapy. Genotyping of all patients was performed using polymerase chain reaction to determine the CYP2D6 (*3, *4, *9, *10, and *41), CYP3A4 (*3, *22), and CYP3A5*3 markers. RESULTS: In the group of patients with moderate symptoms, carriers of the CYP2D6*10 and CYP2D6*41 polymorphisms showed a significantly greater reduction in symptoms according to the overall IPSS score at 8 weeks (p=0.046) and in the micturition symptom subscale starting from 4 weeks of treatment (p<0.05). Carriers of the CYP2D6*10 polymorphism in both groups were associated with a decrease in residual urine volume at 8 weeks (p<0.05). The presence of the CYP3A5*3 variant in those with severe symptoms significantly improved quality of life during therapy. Allelic variants of the CYP2D6 and CYP3A genes did not affect the frequency of adverse events. CONCLUSION: The results obtained by calculating the prognostic significance of individual polymorphic markers pointed to the contribution of CYP2D6*10 and CYP2D6*41. Tamsulosin therapy is more effective in patients with LUTS who are carriers of these allele variants. The safety parameters of tamsulosin were not influenced by the studied polymorphic variants. It was found that CYP3A5*3 was associated with an increase in the subjective assessment of the patient's quality of life, but it is too early to draw final conclusions. The issue of the contribution of genetic factors to the efficiency and safety of treatment of LUTS in BPH requires further study with a larger sample size and analyzed parameters.

[Changes in the structural and functional properties of erythrocytes in serous and purulent acute pyelonephritis].

to establish violations of the structural and functional properties of peripheral blood erythrocytes in serous and purulent acute pyelonephritis before and after conventional therapy. MATERIALS AND METHODS: The structural and functional properties of erythrocytes of 62 patients with various forms of acute pyelonephritis, randomized by age, sex, and the minimum number of concomitant diseases in remission, were examined. Results and its discussion. In serous, to a greater extent, in the purulent form of acute pyelonephritis, violations of the usual ratio of erythrocyte membrane proteins responsible for the flexibility and shaping of the membrane, intracellular metabolism, stabilization and structure formation of the plasma membrane skeleton were established. Disturbances in the lipid content of erythrocyte membranes, which form the basis of the lipid framework of the plasma membrane and play a major role in the ordering of protein macromolecules and normal erythrocyte metabolism, were revealed. CONCLUSION: In the serous and purulent phases of inflammation, disturbances in the qualitative and quantitative variant of the protein and lipid fractions of the membranes cause functional changes in blood erythrocytes that are not normalized by standard treatment in the purulent form of the disease, which requires the development of correction methods.4 CONCLUSIONS: In patients with NDE before treatment, an increase in the level of only one representative of the investigated proteins of the circulating erythrocyte membrane out of 12, namely tropomyosin, was revealed, which can be used in the differential diagnosis of pyelonephritis forms. In patients with a purulent form of pyelonephritis, a more significant increase in lipid peroxidation processes, a weakening of the bodys antioxidant system, and a decrease in the adsorption characteristics of erythrocytes were revealed. Given the lack of effectiveness of basic treatment in relation to most indicators of the structural and functional properties of erythrocytes, it is necessary to include immunomodulatory and antioxidant drugs in the complex treatment for serous and purulent forms of acute pyelonephritis, which will help reduce complications and enhance regenerative processes. RECOMMENDATIONS: to recommend to medical specialists to use indicators of structural and functional properties of erythrocytes in difficult cases of differential diagnosis of forms of acute pyelonephritis.

[The relationship between penile hemodynamic parameters in cavernous rteries and penile rigidity].

INTRODUCTION: Blood flow parameters in cavernous arteries during full-erection phase on Doppler ultrasonography are associated with intracavernosal pressure and, consequently, with penile rigidity. AIM: To examine the relationship between blood flow parameters in cavernous arteries and the penile rigidity. MATERIALS AND METHODS: A total of 54 healthy men and patients with erectile dysfunction of various degrees of severity, with mean age of 43,0 +/- 2,2 years ranging from 18 to 74 years, were included in the study. Erectile function was examined and 81 Doppler ultrasonography were performed after intracavernosal injection of alprostadil (10 mcg). In full-erection phase, peak systolic velocity (PSV) and systolic acceleration (SA) were measured, as well as resistive index (RI). Mean values were calculated for both cavernous arteries. Penile rigidity was assessed in three ways: clinical evaluation according to I. Goldstein, measurement of surface rigidity and evaluation of longitudinal rigidity. RESULTS: During Doppler ultrasonography a strong correlation of penile rigidity with RI (0,71-0,85) and SA (0,63-0,69) was found. Indirect assessment of penile rigidity using PSV values was less precise. With RI values close to 1,0, SA is a more reliable method for indirect rigidity assessment. CONCLUSION: Penile blood flow parameters, RI and SA, allow to evaluate a degree of rigidity and to eliminate subjectivity of the specialist performing the examination, as well as to obtain a range of penile rigidity values.

[The main aspects of the impact of the new coronavirus infection SARS-CoV-2 on the development of infertility in men].

Since the end of 2019, the world has been overwhelmed by a pandemic of a new coronavirus infection (COVID-19), a disease that damages various organs and systems. Because of the extensive coverage of the population by the infection, the long-term effects of the disease are not well understood, which is of considerable scientific and practical interest. We performed an in-depth analysis and systematization of data from foreign and domestic publications in the Scopus, Web of Science, eLIBRARY, PubMed, Wiley Online Library, and Google Scholar databases were performed. Information searches included original articles, reviews, guidelines, manual comments, and editorials related to the effects of SARS-CoV-2 virus on the male reproductive system. Accumulated clinical evidence suggests that the SARS-CoV-2 virus and the COVID-19 disease it causes have a negative impact on male reproductive health.. Drugs with a negative effect on spermatogenesis are used in the therapy of patients with COVID-19. These include lopinavir, chloroquine and its derivatives, and widely used glucocorticosteroids. Lopinavir and chloroquine have subsequently been excluded from potential COVID-19 therapy. Although available data on the fertility of men with COVID-19 are scarce and the results of published studies are from a limited sample, it is clear that maintaining male reproductive health during the COVID-19 pandemic is a pressing issue in modern medicine and requires further in-depth study. Preconceptional screening should be recommended for men who have undergone COVID-19.

[Application of laser technologies in the treatment of non-muscle-invasive bladder cancer].

This review includes the facts of bladder treatment by means of laser technologies application in historical perspective. Advantages and disadvantages of different laser technologies were considered in comparison with the traditional TUR of the bladder wall.

[Molecular genetic predictors of the efficacy and safety of tamsulosin therapy].

Individual differences in efficacy and safety of drugs between patients are a significant problem in modern pharmacotherapy. The bodys pharmacological response to the administration of a particular drug is determined by multiple factors, where up to 50% of the variability of the pharmacological response may be determined by the genetic variability of the body. The article presents an up-to-date review of the data on genetic polymorphisms influencing the efficacy and safety of tamsulosin therapy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.

[Focal laser coagulation in the treatment of a patient with kidney cancer and prostate cancer].

The article describes the clinical observation of the patient 84 years old with prostate cancer T2bNxM0, left kidney cancer T1N0M0 and severe comorbidity. Stepwise interstitial laser coagulation was performed using the Russian microsecond Nd: YAG laser surgical complex.

[Markers of stem cells and their prognostic values for urothelial carcinomas of the urinary tract].

The fundamental question about the origin of cancer stem cells of urothelial carcinomas with luminal remains open. So far, no convincing evidence has been found to determine whether these events occur in a single cell, presumably basal, or are realized in different precursor cells of the urothelium. The potential of a number of potential stem markers as cancer stem cells in urothelial carcinomas and their prognostic significance are currently being investigated. AIM: Our aim was to carry out a comparative analysis of the expression of stem markers in the molecular subtypes of urothelial carcinomas, including ALDH1A1, CXCR4, CD24, CD82, CD105, CD133, NANOG, OCT4 and SOX-2. In addition, the relationship between the pattern of expression and the pathological features of the tumor was determined. PATIENTS AND METHODS: Surgical specimens from 196 patients with a diagnosis of urothelial carcinoma of the renal pelvis and bladder were studied. Immunohistochemical study was performed on paraffin sections using the standard protocol. Antibodies against ALDH1A1, CD82, CD133, CXCR4, NANOG, OCT4, SOX2 ("Abcam"), CD24, CD105 ("Invitrogen"), CD31, CD34 ("Novocastra") were used. RESULTS: The stem cell markers used in the study were expressed in all molecular subtypes of urothelial carcinoma and there were no differences in frequency and intensity of expression between different phenotypes. However, the frequency and intensity of expression of the markers correlated with the tumor stage and the grade of cellular anaplasia. CONCLUSION: Our results confirm that cancer stem cells with basal phenotype are not an exclusive subpopulation in urothelial tumors. Other progenitor cells with the immunophenotype of intermediate and/or umbrella cells can serve as cancer stem cells. These features of the expression in cancer stem cell markers will allow to develop new approaches to the treatment of urothelial carcinomas.

[Interstitial laser coagulation in the management of urothelial papillary carcinoma of the renal pelvis].

This article presents a case of a 59-year-old patient with a primary tumor of the right kidney with bladder and liver metastases. The patient was treated in three-stages. In the first stage, he underwent ureteral stone extraction, laser resection of the tumor with subsequent vaporization. In the second stage, a repeat laser resection and vaporization of the tumor was performed. During the third stage, the patient underwent TUR of the bladder wall with the tumor, followed by laser vaporization of the tumor bed. During a 9-year follow-up, no signs of tumor growth or metastasis were observed.

[Age-related androgen deficiency. The current state of the problem].

This paper reviews the modern concept of age-related androgen deficiency. The authors discuss the prevalence of androgen deficiency and its relationship with age, concomitant diseases, pharmacotherapy and other factors.

[Large urethral stones: a case report].

The article describes a clinical observation of a 68 y/o patient with large stones of the urethra, reaching 5 cm in length and located in the penile urethra. The patient underwent a three-stage treatment: the first stage consisted of drainage of the urinary bladder, the second stage of the urethrolithotomy and a double-barreled fistula, the third was an anastomotic urethroplasty. After removing the cystostomic drainage tube, normal urination was restored.

[EXPERIMENTAL VALIDATION OF ND:YAG LASER COAGULATION OF THE BLADDER TISSUE].

Interstitial laser coagulation (ILC) is one of the minimally invasive and minimally traumatic methods for the destruction of small lesions in various organs and tissues. Selection of the optimal operation and exposure mode is critical for the safe use of ILC in clinical practice. The in-vivo study of ILC effects on bladder tissue was carried out in 6 rabbits weighing less than 3 kg. Macroscopic and microscopic analysis of the tissue was done directly after the ILK procedure, on days 3 and 7, 14 and 21 following specimen collection of experimental animals. Safety and efficacy of ND: YAG laser impact on bladder tissues were confirmed by morphological study, which established phasing and extent of changes in the bladder tissues. The results allow us to recommend ILC application for the destruction of small size bladder tumors without impairment of the bladder functions, as well as for the treatment of bottom after transurethral resection of bladder cancer.

[The use of NefroDoz in patients with urolithiasis who underwent extracorporeal shock wave lithotripsy].

The article presents the results of the multicenter clinical comparative open-label trial in three parallel groups, which was aimed to the evaluation of the efficacy and safety ofbiologically active food supplement NefroDoz after extracorporeal shock wave lithotripsy (ESWL) in patients with urolithiasis. NefroDoz was prescribed for the lithokinetic purpose. The study involved 114 patients from different regions of the Russian Federation aged from 18 to 75 years (mean age 45.56 +/- 12.49 years) with a diagnosis of urolithiasis who underwent ESWL. Patients were divided into 3 groups according to the type oftreatment. Evaluation of the effectiveness was performed using data from a blood test, urine analysis, and biochemical blood assay, ultrasound and KUB X-ray. The results showed that NefroDoz has diuretic, anti-inflammatory, and lithokinetic effects, and is effective and safe drug for the patients with urolithiasis who underwent ESWL.

[Features of endoscopic surgical treatment of urolithiasis in overweight patients].

The article presents the results of endoscopic and nephrolithotripsy and ureterolithotripsy in 73 overweight patients (body mass index of over 30 kg/m2) with kidney stones and urinary tract infections of different locations compared with 30 patients without obesity. The features of choice of tactics of surgical treatment and access, possible complications and their prevention are described.

[Therapy of rapid ejaculation using dietary supplement "NeyroDoz": results of a multicenter non-randomized clinical study].

The main aim of the study was to determine the effectiveness of a multicomponent dietary supplement NeyroDoz in patients with rapid ejaculation. We examined 50 patients with rapid ejaculation (premature ejaculation), who were recruited in 9 clinical centers in different regions of Russia. These patients received NeyroDoz, 2 capsules twice a day for one month, followed by a control observation for 1 month. In study group of patients, symptomatic improvement was achieved in 45 (90%) of 50 patients at 4-week observation target date. In assessing the impact of NeyroDoz on different groups of symptoms, it was found that it significantly increases the average time of sexual intercourse by 2 times, increases the orgasm brightness, reduces the severity of psychosomatic component and has a positive effect on all components of the copulative cycle. In assessing the afterimpression, this effect was maintained throughout the period of follow-up.

[Modern tactics of management of patients with bilateral staghorn nephrolithiasis].

A comparative analysis of the effectiveness of open and percutaneous operations in the treatment of bilateral staghorn nephrolithiasis (SN) was performed. Of the 38 patients with bilateral SN, stage operation (without discharge) was performed in 26 (68.5%) patients, and single-step operation--in 12 (31.5%) patients. For the 47 patients with bilateral SN, who underwent open surgery, the interventions were following: pelviolithotomy (64 operations), nephrolithotomy (21 operations), nephrectomy (9 operations). Surgery was performed in stages on each side, but unlike percutaneous operations, with discharge from the hospital. When using open surgery, only in 27 of the 47 patients complete discharge of kidney stones was achieved. A comparative analysis of single-step and stage surgery for bilateral SN revealed no significant difference in the duration of surgery and intraoperative blood loss (p > 0.1); endoscopic surgery compared with open surgery is characterized by significantly lower intraoperative blood loss and postoperative in-hospital stay (p < 0.001).

[Experimental validation of the use of ND:YAG-interstitial laser coagulation of the kidney].

Interstitial laser coagulation (ILC) is one of the effective methods of minimally invasive destruction of small renal tumors. For the safe use of ILC in clinical practice, it is necessary to select the optimal mode of action of laser radiation on the tissue of target organ and techniques for the procedure. The effects of ILC on kidney tissue in 6 rabbits weighing less than 3 kg and 5 mongrel dogs weighing up to 20 kg were investigated in vivo. The impact of ILC was made intraoperatively. Organ retrieval in experimental animals for the macro- and microscopic examination was performed immediately after the impact of ILC and at various times thereafter during the month in rabbits and 35 days in dogs. Morphological study in different periods after exposure allowed to establish phasing and volumes of changes in the tissues of the kidney, confirming the safety and efficacy of ND:YAG laser irradiation on kidney tissues. The results indicate the possibility of effective application of ILC of kidney tissues for destruction of small size tumors, without impairment of functions of the organ.