[Possibilities of using dietary supplements with antioxidant properties in urinary stone disease].

INTRODUCTION: Dietary supplements are successfully used in many fields of medicine, including urology. In particular, urologists often prescribe dietary supplements for patients with urolithiasis. AIM: to study an influence of dietary supplements Nefradoz on the metabolism of the main stone-forming substances and inhibitors of stone formation in patients with urolithiasis. INTRODUCTION: Dietary supplements are successfully used in many fields of medicine, including urology. In particular, urologists often prescribe dietary supplements for patients with urolithiasis. AIM: to study an influence of dietary supplements Nefradoz on the metabolism of the main stone-forming substances and inhibitors of stone formation in patients with urolithiasis. MATERIALS AND METHODS: A total of 60 patients with urinary stone diseases were included in a single-center prospective randomized study. All patients were divided into 2 groups of 30 people, depending on the treatment. In the main group, patients followed standard diet, received general recommendations and dietary supplements Nefradoz for 28-30 days, 1 capsule (150 mg) 2 times a day with meals. In the control group, patients received only general recommendations and followed standard diet therapy for 28-30 days. The blood biochemical profile and 24-hour urine analysis were evaluated, as well as a urinalysis was performed on daily basis. RESULTS: In patients receiving Nefradoz, urinary uric acid excretion increased by 0.9 mmol/day. It must be emphasized that an increase in uric acid excretion did not exceed the upper normal limit. A tendency towards an increase in urine excretion of sodium (by 54 mmol / day), magnesium (by 1 mmol / day) and citrates (by 0.6 mmol / day) was also found. The analysis of urinalysis showed that in the main group, urine specific gravity was lower than in the control group. Higher urine pH in the main group compared to the control group was also shown. The severity of hematuria with the use of Nefradoz was almost two times lower than in patients who did not receive dietary supplement. CONCLUSION: Considering our data on the ability of dietary supplement Nefradoz to increase the concentration of main inhibitors of stone formation (magnesium and citrates), Nefradoz can be recommended for patients with urinary stone diseases, especially with concomitant hypomagnesuria and hypocitraturia.

Stimulation of Structural and Functional Recovery of the Kidney in Rats with Postischemic Acute Renal Failure of Different Severity by Embryonic Protein-Peptide Complex Therapy.

In male rats, acute renal failure was simulated by clamping the vascular pedicle of the left kidney for 60 or 90 min and right-sided nephrectomy. In the control series, no therapy was performed. In the experimental series, the animals were daily injected subcutaneously with Cellex, a protein-peptide complex (PPC) chromatographically isolated from the brain tissue of pig embryos with a molecular weight of its components from 10 to 250 kDa. PPC was administered 5 times a week (10 injections) in a dose of 0.1 ml/kg (0.1 mg active substance per 1 kg body weight). Ischemia of a single kidney led to the development of acute renal failure, more severe after 90-min ischemia. PPC therapy reduced the severity of functional disorders mainly at the early stages (3 and 7 days) with normalization of blood concentrations of urea and creatinine, creatinine clearance, tubular reabsorption of sodium and calcium, including the cases with 90-min ischemia, which did not occur in the control series. PPC therapy also contributed to hypertrophy of many glomeruli, prevented the development of glomerulosclerosis, and reduced damage to the epithelium of the renal tubules. At the same time, neither pronounced lymphohistiocytic infiltration, nor focal nephrosclerosis typical of control series were observed.

[Prediction of the effectiveness of the therapy of LUTS/BPH by Serenoa repens extracts].

INTRODUCTION: For the treatment of LUTS/BPH is used a wide range of drugs that patients have to take for a long time. Therefore, it is important to develop methods for predicting long-term results of therapy. The purpose of this work is to evaluate the possibility to predict long-term results of drug therapy of LUTS/BPH using mathematical modeling on the example of treatment with Serenoa repens extract (ESR - Permixon). MATERIALS AND METHODS: For prediction using the methods of predictive analytics of the therapeutic ESR effect in the long term, materials from the open study "Clinical and biological long-term tolerance of a lipidosterolic extract of Serenoa repens (Permixon) in patients with symptomatic benign prostatic hypertrophy" (No. P0048 95 GP 401) were used. The study took place in 1995-1999 in 3 Moscow medical centers: Research Institute of Urology of the Ministry of Health of the Russian Federation, Urological Clinic of the Moscow Medical Academy named after Sechenov and the urology department of Moscow Clinical Hospital No 60. The study included 155 patients aged 52 to 87 years (65.3) who received the drug in 320 mg capsules per day for two years. The target indicators of the prognosis identified key clinical parameters: a decrease IPSS of>25% or>3 points and an increase in Qmax>25% at 12 and 24 months of treatment. When evaluating the results, a binary approach was used: improvement achieved (1), not achieved (0). RESULTS: Using the methods of predictive analytics, mathematical models were built to predict the long-term results of treatment according to the most significant 7 initial criterias (predictors): IPSS; Qmax; average urine flow rate; urination volume, urination time, residual urine volume, prostate volume. For each target field and time interval, mathematical models were built using ensembles from 7 selected machine learning algorithms with the best predictive qualities: BNet; C5.0; SVM; KNN; NNet; CHAID; C&RT. Verification of models on internal randomized samples showed their high prognostic properties: sensitivity 82.4-99.0; specificity 75.0-96.1; AUC 0,864-0,965. CONCLUSION: The potential for effective prediction by the methods of predictive analytics and data mining of the separated results of drug therapy of LUTS / BPH according to the main clinical criteria was demonstrated. It is necessary to continue training and testing the model with the inclusion of new clinical observations in the data set. This approach is applicable to the creation of similar models for predicting the effect of other drugs.

[The features of pathogenesis of urolithiasis in patients with diabetes mellitus type 2].

INTRODUCTION: In recent years, a large number of studies has been published that proved a very significant role of diabetes mellitus type 2 for development of urolithiasis. The aim of our work was to conduct a comparative study of biochemical parameters of blood and urine as well as chemical composition of urinary stones in urolithiasis patients in the general population and in patients with diabetes mellitus type 2. MATERIALS AND METHODS: The work was divided into 2 stages. During the first stage an analysis of chemical composition of urinary stones in the general population (n=5669) and in patients with diabetes mellitus type 2 was carried out (n=350). During the second stage an analysis of biochemical parameters of blood and urine in urolithiasis patients in the general population (n=101) and in patients with diabetes mellitus type 2 was conducted (n=350). RESULTS: In the general population calcium oxalate stones was predominated (56.8%), while phosphate (24.9%) and urate (17.4%) stones were less frequent. In a subgroup of patients with diabetes mellitus type 2 uric acid stones were predominated (74.3%), significantly exceeding calcium oxalate (15.1%) and calcium phosphate (10.6%) stones. In the general population of patients with urolithiasis, hypercalciuria, hyperuricosuria, hyperuricemia and hypomagnesiuria was detected in 60.4%, 42.6%, 26.7% and 43.5% of cases, respectively. In patients with concomitant diabetes mellitus type 2, hypercalciuria, hyperuricosuria, hyperuricemia was observed in 9.4%, 26.7% and 42.5%, respectively. In 60.3% of patients with diabetes mellitus type 2 marked acidity of the morning urine was detected (pH<6.0). CONCLUSION: Correction of metabolic disorders in patients with urinary stone disease and diabetes mellitus type 2 should be aimed at increasing of urine pH and reducing the level of uric acid in the blood and urine.

[Nephrolithiasis coexisting with type 2 diabetes: current concept of the features of stone formation and the effects of hypoglycemic therapy on lithogenesis].

The article analyzes Russian and international literature examining specific features of the pathogenesis of renal stones in the setting of carbohydrate metabolism disorders. The authors outline the renal effects of the main pharmacological groups of oral hypoglycemic drugs regarding metaphylaxis of nephrolithiasis. An increased risk of nephrolithiasis in type 2 diabetes mellitus is realized through hyperuricemia with concurrent urine acidification. Current literature is lacking studies on the effects of oral hypoglycemic drugs on urine properties. There are reports about the tendency of biguanides (metformin) to shift the urine reaction to the acid side. Derivatives of sulfonylureas, incretins and inhibitors of dipeptidyl peptidase-4, do not significantly affect the urinary acidity and urinary salt excretion. Inhibitors of sodium-glucose cotransporter type 2 (gliflozins) tend to reduce the blood level of urate, but the mechanism of this effect and the safety of these drugs in the setting of urolithiasis have not yet been investigated.

Role of oxidative stress and mitochondria in onset of urinary bladder dysfunction under acute urine retention.

Acute urine retention is a frequent complication in patients with benign hyperplasia of the prostate gland. According to studies made on experimental animals and people, it is accompanied by the deterioration of the bladder blood supply. This study attempts to explore the relationship of intramural blood flow, production of reactive oxygen species, and functional state of the bladder detrusor in modeling of acute urine retention in rats, as well as the impact of mitochondria-targeted antioxidants (which are supposed to alleviate the effects of oxidative stress induced by experimental ischemia) on these parameters. The study showed beneficial effects of mitochondria-targeted antioxidant SkQR1 in preventing damage of the bladder caused by acute urinary retention, which suggests the therapeutic use of this type of compounds for the treatment of ischemic abnormalities of the urinary bladder.

[Infectious genesis of nephroliths (electron-microscopic study)].

Scanning electron microscopy and x-ray microstructural analysis were employed in the study of nephroliths from patients suffering from nephrolithiasis. Bacterial biofilms, urease producing microorganisms, alkaline reaction of the urine are basic factors for local urine crystallization, formation of the base of the nephroliths and its rigid fixation to the pelvic mucosa. Mechanic trauma of the pelvic tissues by the concrement results in destruction of the pelvic mucosa epithelium at the site of the nephrolith. Subsequent inflammation in the underlying connective tissue contributes to formation of connective tissue commissures fixing the conrement in the kidney. It is shown that bacteria as a part of a biofilm are capable to persist in nephroliths for a long time. Destruction of the stones during operation or lithotripsy can trigger activation of growth of bacteria integrated in the biofilm and cause septic complications. Preservation of commissures with elements of the destroyed stone after lithotripsy or surgical removal is one of the leading causes of recurrent nephrolithiasis.

[Biological aspects of choice of the intestinal segment for the cystoplasty].

Contractile activity of the iliac and sigmoid intestines versus detrusor activity, reabsorption and secretory activity of the iliac and sigmoid intestinal mucosa in contact with urine were studied in 30 rats. It was found that isolated segments of the iliac and sigmoid intestines have spontaneous contractile activity (stronger in the iliac intestine) while bladder segment contracted only in response to electric stimulation. A contraction-stimulating effect of acetylcholine and a relaxing effect of noradrenaline in experiments with the iliac intestine were close to their effects on the detrusor. The sigmoid intestine responded weaker to the above mediators. The iliac mucosa actively reabsorbed urinary urea, creatinin, glucose causing elevation of their concentrations in blood as well as K, Na, Ca, CI, P and secreted protein in urine leading to hypoproteinemia. The sigmoid mucosa showed weaker metabolic activity. The results of the study demonstrate importance of consideration of biological properties of different intestinal regions for choice of a cystoplasty method after cystectomy.

[Tamsulosin in combind treatment of patients with urolithiasis].

In administration of tamsulosine (focusin, Zentiva, Czech Republic) in combined treatment of urolithiasis concrement evacuation after extracorporeal lithotripsy occurred in 83% cases in patients with the concrement stay in the ureter for less than one month. The size of the concrement after successful lithotripsy had no significant effect on subsequent stone-eliminating therapy but long-term stay of the concrement in one place promoted inflammatory and urodynamic disturbances in the ureter treated surgically. The comparative analysis of the contractile function of the distal ureteral comparment in patients given tamsulosin showed a less active (amplitude of the contractions) and passive (tonicity) resistance to urine flow than in patients given a standard therapy. These changes were accompanied with lower pressure in the renal pelvis and suppression of enzymuria. Thus, tamsulosin addition to combined treatment of urolithiasis has a positive effect on ureteral urodynamics, concrement evacuation and functional structures of the kidney by indirectly lowering intrapelvic pressure.

[Mechanism of action and efficacy of litium chloride in thermal ischemia of the kidney].

A protective effect of lithium chloride (LC) in thermal ischemia of the kidney of different duration was studied in rats. LC efficacy was estimated by functional activity of ischemic kidney in early and late reperfusion period, by damage to mitochondria of tubular epithelial cells and production of active oxygen forms (AOF) and nitric oxide (NO). LC has a marked anti-ischemic effect. In thermal renal ischemia for 40 and 60 min LC provides functional safety of the ischemic organ. In longer ischemia, 50% of the animals died. The mechanism of the protective action of LC is related to reduction of APK production, support of a high transmembrane potential of mitochondria and NO synthesis redistribution in the cells of tubular epithelium cells.

Comparative analysis of secretory and reabsorbing activity of ileal and sigmoid mucosa, employed for urinary bladder intestinoplasty.

In experiments on rats we studied reabsorption and secretory activity of the mucosa in isolated segments of the ileum and sigmoid colon used for urinary bladder intestinoplasty after cystectomy. Ileal mucosa was found to retain high metabolic activity under changed conditions. It reabsorbs urea, creatinine, potassium, sodium, chlorine, phosphorus, calcium, glucose, and uric acid from the urine and secretes magnesium, iron, and proteins into the urine. Sigmoid mucosa appeared to be less active in terms of reabsorption of the studied urine metabolites, but more actively secreted calcium and magnesium into urine and additionally secreted sodium. It was accompanied by an increase in blood concentrations of urea, creatinine, glucose, phosphorus, magnesium (only for sigmoid colon) and development of hypoproteinemia. These findings are important for investigation and prevention of metabolic complications after urinary bladder intestinoplasty.

[Assessment of metabolic disturbances risk factors in urolithiasis children with questionnaire survey].

Risk factors of metabolic disturbances in children with urolithiasis were studied in 38 children aged 1.7 to 14 years. The information for the disease history was obtained from the parents of the children participating in the study. The parents filled in special questionnaire which has detected that 14.2% of fathers and 72% of mothers had chronic diseases; when pregnant, 81.5% mothers had toxicosis and gestosis, 23% suffered from various viral and bacterial infections treated for a short time with drugs; 63% mothers did not keep diet before pregnancy but pregnancy and lactation made 77% of them pay due attention to their food and diet regime. Breast feeding lasted for the first 2-6 and 1-2 months in 38 and 50% mothers, respectively. Feeding was mixed from birth in 23% babies. Development of metabolic disturbances in children leading to urolithiasis depends on many factors closely linked with environment pollutants, life style of the parents, gynecological health of mothers, intercurrent diseases. Immunogenetic, hereditary mechanisms are involved in triggering urolithiasis in children.

[The role of the mitochondria generating reactive oxygen species and nitric oxide in postischemic functional disturbance of the kidney].

Experiments on 10 rats and 10 rabbits were made to investigate metabolic aftereffects of 40-minute heat ischemia and subsequent reperfusion. It was found that mitochondrial function deteriorated significantly in an early postischemic period. The disorder manifested with a relative prevalence of cell ATP consumption over its synthesis. This is accompanied with intensive production by mitochondria of nitric oxide and oxygen free radicals. Fluorescent probes and confocal microscopy of vital renal sections showed that mitochondria are responsible for excessive generation of nitric oxide and oxygen radicals in the kidney in an early reperfusion period. The discussion concerns the role of nitric oxide in reperfusion renal damage and participation of mitochondria in formation of its anti-ischemic resistance.

[Effect of mineral water on metabolic processes].

The paper comparatively analyzes the effect of the mineral water "Penta" on the biochemical parameters of blood and urine, which characterize the functional activity of renal metabolic processes. A group comprising 10 examinees without renal disease took water by the routine mineral water scheme for 4 days. Comparison of the biochemical parameters before and after water taking revealed a significant reduction in azotemia and uric acid levels with its simultaneously enhanced excretion, as well as an increasing tendency for the excretion of oxalates, i.e. the most important parameters determining the formation of urate and oxalate calculi. These findings allow use "Penta", to a certain degree, in the treatment of renal disease, urolithiasis in particular, and in the prevention of stone formation.

[Change in indicators of metabolism and kidney function in intact rats after parenteral administration of sodium hypochlorite]. / Izmenenie pokazatelei metabolizma i funktii pochek u intaktnykh krys posle parenteral'nogo vvedeniia gipokhlorita natriia.

The changes of kidney metabolism, function and enzymuria activity of nephron epithelium cells after 4 days of parenteral administration of sodium hypochlorite 0.02% and 0.06% solutions were investigated in the experiments on 15 intact non-inbred rats of 200-280 g body weight. It was revealed that sodium hypochlorite induced metabolic damage to the kidney similar to ischemic one. The 0.02 and 0.06% solutions of sodium hypochlorite administered parenterally produced no negative effect on renal function. There was no significant rise of enzymuria activity in experimental groups compared to the controls. Moreover, enzymuria of four from six nephron epithelium cell enzymes decreased significantly to day 5 of the experiment. Metabolic damage and enzymuria activity changes were more pronounced in rats given parenteral 0.06% solution of sodium hypochlorite.

[Residual kidney stones and their treatment]. / Rezidual'nye kamni pochek i ikh lechenie.

416 case histories of patients with different forms of urolithiasis aged 6 to 70 years who had undergone sectional nephrolithotomy (83, 19.9%), pyelonephrolithotomy (24, 5.8%), pyelolithotomy (146, 35.1%), percutaneous nephrolithotomy (163, 39.9%) were analysed. Residual nephroliths occurred in 108 (25.9%) patients. 98 of them were subjected to extracorporeal lithotripsy (ELT). To determine minimal possible interval between the operation and ELT, changes in the levels of lipid peroxidation products and concentration of alpha-glutathione-S-aminotransferase were studied. The results allowed the authors to optimize ELT after operative interventions for uroliths. In the course of 206 ELT sessions the residual uroliths were destroyed in 96 (97.9%) patients. After one session a complete fragmentation was achieved in 19 (19.4%) patients, after two sessions--in 64 (65.3%) patients, after three sessions and more--in 15 (15.3%). Pyoinflammatory complications developed in 8 (8.2%) patients while retrospectively such complications were encountered in 16 of 50 patients (32%). One month after ELT, the control examination found neither nephroliths nor their fragments in 85 (86.7%) patients, in patients with large and multiple stones elimination rate 1.5 months after the treatment was 69.5%. It is inferred that ELT is an effective method of residual uroliths elimination and is a method of choice in the treatment of such patients.

[Increase in structural-functional tolerance of kidney to ischemia upon parenteral administration of sodium hypochlorite in the pre-ischemic period]. / Povyshenie strukturo-funktsional'noi tolerantnosti pochek k ishemii pri parenteral'nom vvedenii gipokhlorita natriia v predyshemicheskom periode.

The opportunity of raising kidney structural and functional tolerance to ischemia with parenteral injections of 0.06% solution of sodium hypochlorite for 4 days in preischemia period was studied in experiment on 22 non-inbred rats of 200-280 g body weight. 90 minute ischemia was created by ligating the left and right kidney arteries, veins, ureters. Morphological and functional kidney data, enzymuria activity of nephron epithelium cells were registered, 80 and 33% of the rats survived 7 days after ischemia in the study and control groups, respectively. The control animals showed deterioration of the tubules function, high enzymuria. Thus, it is possible to raise kidney tolerance to ischemia by preischemic parenteral injection of sodium hypochlorite solution.

[Gastrointestinal hemorrhage in urological diseases]. / Zheludochno-kishechnye krovotecheniia pri urologicheskikh zabolevaniiakh.

The authors analyse 28 cases of gastrointestinal hemorrhage (GIH) in urological diseases and after uronephrological operations, emphasize factors of uremic intoxication and relevant complications provoking DIC syndrome. Various factors leading to stress (acute blood loss, shock, sepsis) and development of immunodeficiency disturbed morphostructure of gastric and duodenal mucosa and provoked hemorrhage which was stopped most efficiently by fibrogastroduodenoscopy with coagulation of the bleeding vessel. If this operation failed, open surgery was performed. Conservative measures consisted in DIC syndrome management policy.

[Role of biochemical methods in follow-up and treatment of patients with urolithiasis]. / Rol' biokhimicheskikh metodov v dinamicheskom nabliudenii i lechenii bol'nykh mochekamennoi bolezn'iu.

4-6-year follow-up using different tests covered 15 patients with urolithiasis and 11 control subjects aged 25 to 66 years. All the patients underwent 1 to 5 sessions of extracorporeal lithotripsy and one patient underwent open surgery. Clinical and biochemical findings on the groups were compared to the evidence of Litos test. Initiation of antirecurrence therapy should be based on the information gained with different methods, primarily, biochemical. Follow-up of the patients including biochemical control over their metabolic condition must be conducted for at least 5 years.