[Herpes viruses and human papillomavirus in prostate cancer: first results].

INTRODUCTION: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are among the most common urological diseases in men. It has been repeatedly suggested that viral infection plays an important role in prostate carcinogenesis. AIM: To assess the relationship between viral infection and PCa, as well as the clinical and morphological features of BPH and PCa. MATERIALS AND METHODS: A total of 98 patients undergoing treatment for BPH (n=48) or PCa (n=50) between 2019 and 2021 were included in the study. Real-time PCR on the surgical specimens for human papillomaviruses (HPV), herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes virus type 6 (HSV-6) was performed. RESULTS: In patients with PCa, viruses in prostate tissue were found more often compared to those with BPH (50.0 vs. 31.3%, respectively, p=0.046.) The most common virus in both PCa and BPH was EBV (22.0 vs. 16.7%, respectively). The second most common virus in patients with PCa was HSV-6 (20.0%), which was not detected in any men with BPH (p=0.003). There was a trend toward higher prevalence of CMV among patients with PCa (16.0% vs. 4.2%), but the difference was not significant (p=0.09). There was no association of viral infection with clinical and morphological features. CONCLUSIONS: The resulting trend toward a higher prevalence of HSV-6 and CMV in patients with PCa compared to those with BPH creates the prerequisites for further study of viruses in prostate diseases involving a larger cohort, which will provide an idea of the multi-stage process of malignant transformation and, possibly, open new therapeutic options for prevention and treatment.

[Efficacy of fesoterodine for prevention of autonomic dysreflexia in patients with neurogenic dysfunction of the bladder after spinal cord injury].

AIM: to evaluate the effectiveness of fesoterodine for the prevention of autonomic dysreflexia (AD) in patients with neurogenic bladder dysfunction (NBD) after spinal cord injury (SCI). MATERIALS AND METHODS: a total of 53 patients with AD were included in the study. In the main group (n=33) patients received fesoterodine 4 mg per day for 12 weeks as a treatment for neurogenic bladder dysfunction and prevention of AD. In the control group (n=20), patients were monitored for 12 weeks without specific treatment. The assessment was based on the results of ADFSCI and NBSS questionnaires, daily blood pressure monitoring with the completion of a self-observation diary, cystometry with simultaneous monitoring of blood pressure and heart rate. RESULTS: In the main group there was a significant decrease in episodes and severity of AD according to ADFSCI questionnaire and an improvement in the quality of life according to NBSS questionnaire compared to the control group (p<0.001). Also, in the main group, the number of episodes of AD and systolic blood pressure decreased. The maximum bladder capacity and bladder compliance increased (p<0.001), and the maximum detrusor pressure and systolic blood pressure when the cystometric capacity was reached, decreased significantly (p<0.001) in the main group compared in comparison with the control group. CONCLUSION: Fesoterodine at a dosage of 4 mg for 12 weeks reduced the severity of symptoms of AD in patients with SCI and NBD, which was manifested by the stabilization of blood pressure and a decrease in the number of episodes of AD, which significantly improved the quality of life. Also, the drug led to a significant improvement in urodynamic parameters during cystometry, in the form of a decrease in detrusor pressure and an increase in cystometric capacity. We can conclude that fesoterodine is effective in the prevention of AD in patients with NBD after SCI.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy.

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

[Phenotyping of angiotensin-converting enzyme in the prostate in patients with prostate cancer and benign prostatic hyperplasia].

BACKGROUND: Angiotensin-converting enzyme (ACE) is expressed by all epithelial cells of the human body. Although the main proportion of ACE is synthesized by the lungs, in men, ACE is also secreted by the testes (testicular form), seminal vesicles and the prostate. In semen, the level of ACE is up to 50 times higher than in blood plasma. The substitution of highly specific epithelial cells of the prostate by tumor cells causes a dramatic decrease in ACE production by the prostate cells. AIM: To assess the possibility of using prostatic ACE as a new marker of prostate cancer (PCa). MATERIALS AND METHODS: ACE phenotyping in prostate of patients with PCa and benign prostatic hyperplasia (BPH) included measurement of the activity of two ACE substrates (HHL and ZPHL); calculation of the ratio of their hydrolysis rates (ZPHL/HHL ratio); quantitative assessment of the ACE immunoreactive protein, the ratio of the immunoreactive protein to the ACE activity, as well as the conformation of ACE using a panel of monoclonal antibodies (mAb) to different epitopes of ACE. RESULTS: ACE activity in tumor cells was markedly reduced and the ratio of immunoreactive ACE to its activity increased. The ratio of the hydrolysis rates of two substrates (ZPHL/HHL ratio) in patients with PCa increased compared to control group, while it was not observed in the vast majority of patients with BPH. There were several tissue samples with a histological diagnosis of BPH, but ACE phenotype was typical for PCa. DISCUSSION: Since a decrease in ACE activity was found in all patients with PCa, we suggest that it may serve as a reliable and early marker of the tumor development. Changes in the ACE phenotype, which are typical for PCa, but found in patients with BPH, may indicate earlier malignant changes in prostate cells, which are not visible on routine prostate biopsy. CONCLUSIONS: ACE activity and its conformation in prostatic biopsies has the potential to be an early biomarker or a differential criterion for PCa. In PCa, the ACE activity in the prostate is significantly reduced, and the ZPHL/HHL ratio is markedly increased in comparison to control group. However, there were no such changes in patients with BPH. In hyperplastic processes of the prostate (BPH, PCa), there is a change in ACE sialylation, which is accompanied by an increase in the binding of ACE to mAb 3F10 compared to the control group. Patients with negative biopsy result, but properties of prostate ACE, which are typical for PCa, require close follow-up, since they may have an increased risk of subsequent developing PCa. However, due to a small sample of patients, the diagnostic potential of prostate ACE for PCa and BPH requires to be validated in a larger number of patients to confirm its predictive accuracy.

[A comparative characteristics of treatment results of patiens with benign prostatic hyperplasia in combination with hypogonadism].

AIM: to compare the efficiency of monotherapy with -blockers vs combined therapy (-blockers in combination with Androgel) in patients with BPH and hypogonadism. MATERIALS AND METHODS: a total of 60 men with BPH and hypogonadism, who were randomly selected from outpatient department were included in the study. All patients were divided into 2 groups (n=30). In Group 1 patients received silodosin, while in Group 2 men were prescribed to silodosin plus Androgel 1% topically. The duration of therapy was 6 months. The results of treatment were evaluated during baseline assessment and further visits every 2 months after starting therapy (total 4 time points). RESULTS: according to the ICEF-5 questionnaire, in the Group 2 an improvement in sexual function domain score (from 6.3 to 26.8 points) was shown. In addition, in combination group there were significant changes in PSA level (from 2.25 to 1.8 ng/ml), prostate volume (from 55.1 to 61.3 cm3), residual urine volume (from 72 to 19 ml), urine flow rate (from 13.34 to 21.1 ml/s), waist circumference (from 116 to 103.2 cm) and body mass index (from 35.4 to 27.2 kg/m2), while in monotherapy group none of these indicators significantly improved. CONCLUSIONS: the use of topical hormone replacement therapy in combination with -blockers in patients with BPH and concomitant hypogonadism is justified and effective in comparison with monotherapy with -blockers.

[Herbal preparations and microelements as alternative therapy in benign prostatic hyperplasia, lower urinary tract symptoms and erectile dysfunction].

The aim of the work is to provide a current view on the efficiency of the components of dietary supplement Antiprost for the treatment of urological diseases. The study results on the influence of the dietary components of supplement Antiprost are presented in the article in according to principles of evidence-based medicine. Antiprost can be used in the routine urological practice in specific situations, e.g., if patient refuses from the conventional treatment in BPH/LUTS/ED for any personal reasons, or in case of individual intolerance of standard drugs. Randomized clinical trials should be performed for further studying of the efficiency of dietary supplement Antiprost.

[Biomarkers of prostate cancer and potential for using ace produced in prostate gland for diagnosis of prostate cancer and benign prostatic hyperplasia].

Prostate cancer (PCa) is the 4th most commonly diagnosed cancer in the male population and incidence of different stages is increasing every year. The efficiency of PCa treatment is strongly dependent on the its stage. Prostate Specific Antigen (PSA) is the most widely used and universal biomarker of PCa worldwide. Considering its limited predictive value, particularly in patients older than 50 with PSA level ranging from 4.5 to 10 ng/ml, there is a need to introduce new serum biomarkers of PCa. Current data on different PCa biomarkers are reviewed in the article as well as a role of angiotensin-converting enzyme (ACE) as a novel PCa biomarker.

[A novel method for non-invasive mechanical ablation of prostate tumors using pulsed focused ultrasound].

AIM: of the study: demonstrate the feasibility of non-invasive mechanical disintegration of human prostate tissue using pulsed high-intensity focused ultrasound (pHIFU), a method termed boiling histotripsy. MATERIALS AND METHODS: An ultrasound experimental system was developed for producing localized mechanical lesions in ex vivo biological tissue samples under ultrasound guidance. A series of experiments was carried out to create small single-focus lesions (volume < 2 mm3) and one large lesion (volume > 50 mm3) in ex vivo prostate tissue samples. After irradiation, two samples were bisected to visualize the region of destruction; the other tissue samples were examined histologically. RESULTS: During pHIFU irradiation under B-mode ultrasound guidance, a region of increased echogenicity caused by formation of vapor-gas bubbles was visualized in the target region. After exposure, small and large lesions filled with a suspension of liquefied tissue were observed. Histological examination confirmed that the prostate tissue in the focal region was disintegrated into subcellular fragments. CONCLUSION: A pilot study showed the feasibility of using boiling histotripsy as a non-invasive method for treating prostate diseases.

[Functional activity of leucocytes in seminal fluid of patients with pathospermia].

OBJECTIVE: Assessment of leukocyte activity as the main source of ROS in seminal fluid of patients with normospermia and pathospermia using an original protocol based on the kinetic chemiluminescence method and adapted for semen analysis. MATERIALS AND METHODS: A prospective study was attended by 95 men of reproductive age who applied to the Research Center of Medical Genetics (Moscow) for semen analysis. The material for the study were samples of native ejaculate. Chemiluminescent measurements were performed on a Lum-1200 chemiluminometer (DISoft, Russia) using the original method. RESULTS: Both in amplitude of basal and stimulated response, between the "normozoospermia", "pathozoospermia" and "pathozoospermia + leucospermia" groups, significant differences were obtained in the level of ROS production by leukocytes (p<0.05): the median level of basal chemiluminescence, normalized on the count of leukocytes was 0.13, 0.71 and 1.78, respectively; the median level of stimulated chemiluminescence normalized to the number of leukocytes was 0.62, 2.14, 5.94, respectively. The level of stimulated response did not exceed 0.5 arb. units in normozoospermic samples. In pathospermic groups, the level of stimulated response was low in about a third of semen samples, it was moderate in one third of patients, and high in one third of patients. CONCLUSIONS: A protocol previously developed for blood analysis was adapted to analyze the total ROS level produced by leukocytes in seminal fluid. In the groups of "pathozoospermia", "pathozoospermia + leucospermia", the level of basal ROS production by leukocytes was about 5 and 15 times higher than in the "normozoospermia" group, the level of stimulated ROS production was 3.5 and 9.5 times; this indicates oxidative stress, including with a normal number of leukocytes.

[Changes in the concentration of urolitiasis markers depending on stone-forming activity in patients with recurrent urolithiasis].

The study aimed to investigate the changes in the concentration of bikunin, osteopontin, and nephrocalcin, depending on the changes in the renal stone-forming activity in patients with recurrent urolithiasis. MATERIALS AND METHODS: The study comprised 152 patients with recurrent calcium oxalate stones at various localizations. Patients of the study group (n=78) were administered complex preventive treatment (water load, Blamaren, thiazide diuretics, oral calcium supplementation) aimed at reducing the activity of urolithiasis. Patients of the control group (n=74) received no treatment. The studied parameters included concentrations of urine bikunin, osteopontin, and nephrocalcin in using ELISA. The follow-up period was six months. RESULTS: By the end of the follow-up, the bikunin concentration in the control group was significantly higher than in the study group (7.0+/-0.81 mg/ml vs. 3.28+/-0.86 mg/ml, respectively, p<0.05) while osteopontin level was significantly lower (2.4+/-0.39 mg/ml vs. 3.4+/-0.36 mg/ml, p<0.05). The nephrocalcin concentrations during the follow-up period did not change significantly (p>0.05). The presence of hypercalciuria did not lead to significant changes in the concentration of stone formation inhibitors. DISCUSSION: The increase in bikunin concentration in control patients is associated with an increase in the expression of this stone formation inhibitor due to the rise in the urolithiasis activity. Reduction in the osteopontin concentration in patients with high urolithiasis activity is a consequence of osteopontin being a constituent of calcium oxalate stones. CONCLUSION: In patients with calcium oxalate urolithiasis, testing for urine concentrations of bikunin and osteopontin as potential markers can be used to estimate the risk of stone recurrence.

[Antioxidative activity and clinical efficiency of dietary supplements Nefradoz for treatment of recurrent calcium oxalate urolithiasis].

AIM: to evaluate antioxidant properties of dietary supplements Nefradoz, as well as its role in the prevention of calcium oxalate stones. MATERIALS AND METHODS: Our study consisted of two parts, clinical and experimental. In the clinical trial a total of 80 patients with recurrent calcium oxalate urolithiasis of various localization were included. All patients were divided into 2 groups. In treatment group (n=45) patients received Nefradoz 1 capsule 2 times a day. In control group (n=35) no treatment was prescribed. In all patients a biomarkers level (bikunin, osteopontin, nephrocalcin) in urine was determined by ELISA. In addition, Litos-test was performed. Follow-up duration was 6 months. In the experimental part of the study, the antioxidant properties of Nefradoz were evaluated using chemiluminescence method. RESULTS: The antioxidant activity of resveratrol, which is contained in 300 mg Nefradoz (1 capsule), was 23.66+/-1.18, which corresponds to the moderate activity. After 6 months of therapy a level of bikunin and osteopontin did not significantly changed, which indicates a minimal risk of stone recurrence. According to the Litos-test, the activity of stone formation in Nefradoz group significantly decreased to minimal values in 42 out 45 patients (p<0.05). In the control group an excretion of biomarkers was minimal, which significantly increased the risk of stone formation. CONCLUSION: Dietary supplement NefraDoz can be used for prevention of calcium oxalate urolithiasis in case of increased stone formation according to the Litos-test. The antispasmodic, uroseptic and diuretic effects allow to maintain the effective level of biomarkers which is required for a recurrence-free course of urolithiasis compared to the control. The antioxidant activity, primarily determined by the resveratrol, can sufficiently compensate for oxidative stress and prevent the development of calcium oxalate stone. Further studies are needed to confirm our results.

[The role of the Randalls plaques in the pathogenesis of recurrent urolitasis].

The aim of the work was to present current concept of the pathogenesis of urolithiasis. Treatment and prevention of this disease a challenging issue. The article presents basic information about Randalls plaques that are described as calcium salt deposits on the surface of the transitional cell epithelium. The cause of Randalls plaques was the subject of many studies and is still not completely clear. To date, we can state that the deposit formation starts in the pelvicalyceal system and is directly linked to recurrent urolithiasis. The discovery of Randall plaques in the 1940s transformed the conception of stone formation, but there are even more questions about the pathogenesis of urolithiasis. In that respect, we consider it important to analyze the studies on Randalls plaques.

[Results of a multicenter non-interventional study on the efficacy and safety of NeyroDoz complex for sexual dysfunction in men].

The article presents the results of a multi-center observational study carried out in 2014-2015 comprising 630 male patients from 23 Russian health care institutions. The study aimed to accumulate epidemiological data on sexual dysfunction in men and test the efficacy and safety of biologically active complex NeyroDoz. Data for the study were collected using questionnaires. The study findings showed a high prevalence of premature ejaculation (PE) in 38.2% of patients with chronic prostatitis (CP) and in 33.25% of patients with erectile dysfunction (ED). The data were analyzed for the total study population (n=630) and separately for three groups of patients selected according to the presence of PE (n=582), orgasmic disorders without PE (n=17) and increased anxiety related to urological diseases without PE (n=31). In all patients of the study, NeyroDoz intake produced a statistically significant increase in the intensity of orgasm from 5,0+/-2,2 to 7,6+/-1,8 points, duration of sexual intercourse from 3,3+/-5,4 to 6,5+/-4,8 min, and satisfaction with sexual intercourse from 1,4+/-0,7 to 3,1+/-1,1 points. In 81% of PE patients the duration of penetration phase of sexual intercourse increased by 50% of the baseline values. The intensity of orgasm increased on average by 60% and 75% in men with PE and orgasm disorders without PE, respectively. Reduction of psycho-emotional burden was observed in 90% of patients with anxiety and depression. The dietary supplement NeyroDoz showed clinical efficacy and safety in the combined treatment of sexual dysfunction in men.

[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.

[Combined treatment of patients with erectile dysfunction and urination disorders].

The article presents the results of the study aimed to the evaluation the efficacy of combination therapy with alpha1-blocker (tamsulosin) and phosphodiesterase type 5 inhibitor (sildenafil) in patients with urination disorders and erectile dysfunction (ED). A pilot observational study involving 60 men aged from 50 and 80 years divided into 3 groups of 20 people was performed. Group 1 of patients received sildenafil 25 mg daily (dynamico), Group 2--tamsulosin 0.4 mg daily (Omnic-Ocas), and Group 3--tamsulosin 0.4 mg (Omnic-Ocas) and sildenafil 25 mg (dynamico) daily. The visits were carried out at the stage of screening, further--every 10 days (a total number--4 visits). Combination therapy of urination disorders and ED contributed to the significant improvement in uroflowmetry, the stopping of complaints according to the IPSS and IIEF-15 questionnaires, and improving the quality of life (according to the QoL questionnaire). Combination therapy significantly decreased obstructive and irritative symptoms, increased the maximum urine flow rate within the period of observation, as well as significantly decreased the residual urine volume, more pronounced when compared with monotherapy. Significant positive effect on erectile component and all components of the overall satisfaction in the sexual sphere were registered, that as a consequence led to the positive impact on the quality of life in patients treated with PDE5 inhibitor. Given the high prevalence of urinary disorders and erectile dysfunction, combined therapy with alpha1-blockers and PDE5 inhibitors in this case should be a promising area for drug therapy.

[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.

[The use of ProstaDoz in patients with chronic prostatitis. Results ofa multicenter nonrandomized clinical study].

The main purpose of the study was to determine the effectiveness of a multicomponent dietary supplement ProstaDoz in patients with chronic prostatitis. The study included 50 men with clinical symptoms of a chronic prostatitis, which were observed in 9 clinical centers in different regions of Russia. All patients have received 2 capsules of ProstaDoz twice a day for 1 month, followed by dynamic observation for 4 weeks. Symptomatic improvement was achieved in 46 (92%) patients. Evaluation of effects of ProstaDoz on various groups of symptoms has revealed that it reduces pain, promotes urination normalization and improvement of quality of life. These effects were maintained during all follow-up period.

[Long-term results of prostatic photoselective vaporization in the treatment of prostatic adenoma].

Assessment of long-term efficacy and complications of prostatic photoselective vaporization (Green Light PV (tm) device, Laserscope, 80W; laser cystoscope, Olympus) was performed in 40 patients with prostatic adenoma (PA) treated in 2005-2006. Mean follow-up was 30.6 +/- 16.6 (5.2-60.6) months, time of operation--52.4 min, intraoperative blood loss--52 ml maximum, duration of bladder draining with catheter--1.15 days. For 12 postoperative months IPSS and QoL declined, then for up to 60 months these parameters went up. An 11-month postoperative follow-up recorded a 68.6% maximal decrease in prostatic volume (the size of the prostate decreased to 22.6 cm3), but after 4 years this volume increased by 24.6% to 38.8 cm3. Qmax increased more actively during postoperative year 1 and reached maximal value to postoperative month 36. Residual urinary volume fell to initial 95.7 ml to minimal 24.8 ml on follow-up month 12. Mean quantity of energy reached 206 +/- 94 (2.4-619.0 kJ. Eleven patients had to take oral anticoagulants without any serious intra- or postoperative complications. Recurrent adenoma rose in 4 patients, urethral stricture--in 6.8% patients, cervical bladder sclerosis was found in 3.6% cases. Prostatic cancer development was not registered. Thus, prostatic photoselective vaporization is a safe and efficave procedure in PA treatment.

[Building of defects of the bladder wall by membrane, created on the basis of type I collagen (an experimental study)].

Experimental study was performed on 24 Chinchilla rabbits, which underwent resection of the bladder with building of defect by membrane "Collost", created on the basis of type I collagen. The functional state of the bladder in situ was assessed by infusion cystomanometry during repeated surgery at 7, 14 day and at 1, 3, 6 months, and at 1 and 1.5 years. It is found that developing detrusor pressure during bladder contractions was decreased by 10 times in the first week of the study; it was in line with the subcompensation after 3 months, and was restored at 6 month. At 1 and 1.5 years, increase of cumulative function of bladder while saving detrusor pressure was observed. Dilating cystoplastics using biopolymer "Collost" provides good long-term functional results.