[Determination of toxic element concentrations in flour and cereal products by mass spectrometry with inductively coupled plasma].

Systemic control and monitoring in the sphere of providing sanitary epidemiological welfare of population require routine procedures for determining toxic elements in variable foodstuffs. Their development is a pressing issue. Our research goal was to develop a procedure for determining concentrations of arsenic, cadmium, lead, mercury, aluminum and strontium in flour and cereal products by mass spectrometry with inductively coupled plasma. Material and methods. The most relevant calibration parameters for an Agilent 7900 mass spectrometer with octopole collision/ reaction cell and conditions for sample preparation by microwave digestion have been established; calibration characteristics and a range of determined concentrations have been identified. The limits of detections (LOD) and limits of quantification (LOQ) for 6 analyzed elements have been calculated. Results. Our procedure for determining mass concentrations of arsenic, cadmium, lead, mercury, aluminum and strontium in flour and cereal products by mass spectrometry with inductively coupled plasma has yielded the following results: when analyzing a sample weighing 0.5 g, we determine cadmium concentration within a range from 0.0008 to 70.0 mg/kg with inaccuracy from 14 to 25%; arsenic concentration within a range from 0.002 to 70 mg/kg with inaccuracy varying from 11 to 26%; mercury concentration from 0.003 to 7.0 mg/kg with inaccuracy from 15 to 25%; lead concentration from 0.01 to 70.0 mg/kg with inaccuracy from 12 to 26%; aluminum concentration from 0.2 to 70.0 mg/kg with inaccuracy from 13 to 20%; strontium concentration from 0.02 to 70 mg/kg with inaccuracy from 12 to 20%. The procedure was tested on samples of rice groats with the focus on the most popular brands. Thus, arsenic was detected in a concentration equal to 0.163 mg/kg in round-grain rice and 0.098 mg/kg in parboiled rice, which does not exceed the permissible level fixed for the element at 0.2 mg/kg. In all the analyzed samples, content of cadmium, lead and mercury did not exceed maximum permissible levels established by the Technical regulation of the Customs Union TR CU 021/2011 for flour and cereal products. These levels are 0.1 mg/kg for cadmium, 0.5 mg/kg for lead and 0.03 mg/kg for mercury. Conclusion. The developed procedure for determining toxic elements in flour, cereals and bakery products by using mass spectrometry with inductively coupled plasma gives an opportunity to determine such elements in quantities lower than permissible levels fixed for them in technical regulations and sanitary rules. The procedure expands the existing methodical instruments for control of food quality in the Russian Federation.

[Molecular Diagnostics of the Involvement of Visually Normal Mucosa in the Malignancy Process in Urothelial Bladder Cancer].

Immunofluorescent method by flow cytometry was used to quantify the expression of the tumor-associated protein ßIII-tubulin (TUBB3) in the tissue of urothelial bladder cancer and visually normal mucosa (56 samples in total). The expression of the marker was detected in 100% of cases, and heterogeneity of the TUBB3 expression level both in tumor tissue and in "normal" mucosa was revealed. The level of TUBB3 in the "normal" mucosa did not depend on the distance from the tumor (1 cm or more than 3 cm) and, on average, it was lower than in the tumor tissue (21.8 ± 10.8% and 24.9 ± 13.2% vs 35.2 ± 12.4%; p = 0.04 and 0.005, respectively). An increase of the TUBB3 expression in the tumor and in the "normal" mucosa was revealed in muscle invasive bladder cancer compared to non-muscle invasive bladder cancer. Therefore, in urothelial bladder cancer, the tumor-associated protein TUBB3 is a molecular marker of bladder mucosa involvement in the malignancy process and predicts the risk of tumor muscle invasion, which may influence indications for early cystectomy.

Biodistribution of Detonation Synthesis Nanodiamonds in Mice after Intravenous Administration and Some Biochemical Changes in Blood Plasma.

Biodistribution of nanodiamonds in mice after intravenous administration, activities of AST and ALT, and the level of bilirubin in the blood plasma were studied in 2.5 h and 10, 35, and 97 days after injection of nanodiamonds. In 2.5 h after intravenous injection, nanodiamonds mainly accumulate in the lungs and liver. Then, redistribution of nanodiamonds from all organs to the liver was observed. Activities of AST and ALT and the level of bilirubin in the blood increased after 2.5 h and then decreased to the initial values.

[Anti-inflammatory activity of high and low methoxylated apple pectins, in vivo and in vitro].

One of the possible mechanisms of the anti-inflammatory action of pectins is associated with the inhibition of excessive pro-inflammatory activity of macrophages - the cells that regulate inflammation intensity and reparative regeneration. It has been found that pectins with a low degree of methyl esterification of the carboxyl groups of the galacturonan core of the macromolecule exhibit this effect. In addition to leukocytes, intestinal epithelial cells are also involved in the pathogenesis of inflammatory bowel diseases. However, to date, there have been insufficient studies of the effect of pectin methyl esterification on the inflammatory response of enterocytes. The aim of the research was to evaluate the effect of the degree of pectin methyl esterification on inflammation of the colon in mice after oral administration and on the inflammatory response of human colon epithelium cells of the Caco-2 line in vitro. Material and methods. In a prospective study, 40 male BALB/c mice weighing 20-25 g were used, 10 animals in each group. Solutions of apple pectins (200 mg/0.2 ml) were orally administered to mice through a plastic catheter 24 h before the induction of colitis. The control mice received water, and prednisone administration at a dose of 5 mg/kg of body weight was used as a positive control. Colon inflammation in mice was induced by a single rectal administration of 5% acetic acid (0.1 ml). A day later, the degree and area of the lesion was assessed using a light microscope, the activity of myeloperoxidase in the wall of the colon was determined by spectrophotometry. The effect of pectins on metabolic activity, intercellular permeability, Tumor Necrosis Factor α generation and alkaline phosphatase (ALP) activity in Caco-2 cells was assessed. Results. It was found that low-methyl esterified pectin AU701, which contains more than 70% of free carboxyl groups, inhibited colon inflammation in mice. High methyletherified pectin AU201, in which more than 70% of the carboxyl groups are replaced by methyl ester, didn't affect inflammation. It was revealed that pretreatment of Caco-2 cells with AU701 and AU201 pectins prevented lipopolysaccharide-induced increase in intercellular permeability and reduced the pro-inflammatory response of Caco-2 cells to LPS. After incubation of Caco-2 cells with AU701 pectin, the rate of hydrolysis of p-nitrophenyl phosphate (an alkaline phosphate substrate) increased by 40%. Pectin AU201 had no effect on the alkaline phosphatase activity of enterocytes. Conclusion. Thus, it was found that low-methyl esterified pectin AU701 inhibits inflammation both in vivo and in vitro. High-methyl esterified pectin AU201 suppresses pro-inflammatory reactions only in vitro. The ability of pectins to inhibit intestinal inflammation has a multifactorial nature, and is due, inter alia, to their ability to stimulate the expression of alkaline phosphatase by enterocytes.

137Cs and plutonium isotopes accumulation/retention in bottom sediments and soil in Lithuania: A case study of the activity concentration of anthropogenic radionuclides and their provenance before the start of operation of the Belarusian Nuclear Power Plant (NPP).

Knowledge of the background activity concentrations of anthropogenic radionuclides before the start of operations of the new nuclear facilities in Belarus is of great value worldwide. Inland water bodies in Lithuania (specifically the Neris River, the Nemunas River and the Curonian Lagoon) are near the site of the Belarusian NPP under construction and, for this reason, sediments and flooded soils from these sensitive areas were analysed for radiocesium and plutonium isotopes (macrophytes were analysed only for 137Cs) in 2011-2012. The 137Cs and 239+240Pu activity concentrations in bottom sediments from the Nemunas River, sampled in 1995-1996 and re-calculated to the year 2016, were compared with those of 2011-2012. The obtained activity of 137Cs in bottom sediments of the Nemunas River and Curonian Lagoon varied from 1 Bq/kg to 47.0 Bq/kg. The activity of 137Cs in the tested soils ranged from 5.3 B g/kg to 32.9 Bq/kg. The 239+240Pu activity in bottom sediments of the studied sampling sites varied between 0.016 and 0.34 Bq/kg and in flooded soils from 0.064 to 0.55 Bq/kg. The 238Pu activity values were very low or lower than the detection limit. The activity of 137Cs in macrophytes varied from values lower than the detection limit to 6 Bq/kg. A strong positive linear correlation for bottom sediments was calculated between: 239+240Pu and total organic carbon (TOC), r = 0.86, p-value 0.01; 239+240Pu and silt, r = 0.80, p-value 0.029; 137Cs and silt, r = 0.78, p-value 0.04; and 137Cs and TOC, r = 0.85, p-value 0.015. The similar peculiarities of 137Cs and 239+240Pu accumulation in bottom sediments and flooded soil allow us to assume that 137Cs can be used as a tracer for 239+240Pu in the initial stage of searching for radionuclide accumulation zones. A remaining impact of the Chernobyl fallout in average comprised: in the Lower Nemunas River and Curonian Lagoon sediments - 51%, in the Middle Nemunas River -90% and in the floodplains of the Nemunas River - 59%, while the provenance of plutonium in studied bottom sediments and flooded soil was the global fallout.

[Novel agonists of melatonin receptors as promising hypotensive and neuroprotective agents for therapy of glaucoma]. / Novye agonisty melatoninovykh retseptorov kak perspektivnye gipotenzivnye i neiroprotektornye sredstva dlia terapii glaukomy.

Melatonin is a pineal hormone that has a capacity to lower intraocular pressure; it exhibits neuroprotective and antioxidant properties that make it possible to use melatonin in the therapy of glaucoma. Analogs of melatonin having affinity to melatonin receptors are promising candidates for application as antiglaucomatous drugs. Chemical modification of the melatonin structure can in-crease efficiency, bioavailability and selectivity of these analogs. We have designed and synthe-sized a number of new 2-oxindole derivatives - ligands of melatonin MT3 subtype receptors that displayed ability to lower intraocular pressure in normotensive rabbits and high antioxidant activity against hydroxyl radical and superoxide anion-radical. The antioxidant activity of new ligands was several times higher than one of melatonin that makes them prospective therapeutic tools for the diseases that include oxidative stress. The maximal hypotensive effect of analogs was comparable to that of melatonin itself but prolonged. Combination of these properties gives an opportunity of using the presented melatonin analogs in complex therapy of glaucoma.

Detection of nanodiamonds in biological samples by EPR spectrometry.

In model experiments in vitro, the applicability of the EPR spectrometry method for the detection of modified nanodiamonds (MNDs) in blood and homogenates of mouse organs has been established. A characteristic signal (g = 2.003, ΔH ≈ 10 G) is observed in the samples of biomaterials containing MNDs, the intensity of which increases linearly with the concentration of nanoparticles in the range of 1.6-200 µg MNDs per 1 mL of the sample. The EPR method in biomaterials reveals the presence of intrinsic paramagnetic centers, signals from which are superimposed on the signal from the MNDs. However, the intensity of these signals is small, which makes it possible to register the MNDs using EPR spectrometry with the necessary accuracy. The data obtained open up the prospects of using the EPR method for studies of the interorgan distribution, accumulation, and elimination of MNDs during their intravenous injection into experimental animals.

SNP Polymorphism in Genomes of CC320 Isolates of Streptococcuspneumoniae Resistant to Beta-Lactams.

Bioinformatic analysis of the data on the genome sequencing of the isolates of the Streptococcuspneumoniae clonal complex SS320 from the Russian Federation, as well as the data on SS320 isolates from public sources in the penicillin resistant isolates resulted in detection of 139 missense mutations in 45 genes. In addition to the mutations in the genes of the main penicillin-binding proteins (PSB - PBP1A, PBP2B and PBP2X) there was detected high frequency of mutations in the genes of the (division and cell wall) dcw-cluster, as well as in RegR protein belonging to the transcription regulators of the LacI/GaIR family. Development of resistance to beta-lactams in S.pneumoniae is defined not only by modification of the PSB, but also by adaptive changes in the metabolic pathways involved in the bacterial cell growth and division.

[METHODOLOGY FOR THE ASSESSMENT OF THE IMPACT OF THE ATMOSPHERIC AIR POLLUTION ON THE FORMATION OF THE LEVELS OF OVERALL MORBIDITY RATE OF BRONCHIAL ASTHMA].

In large cities with strong air pollution the formation of the levels of morbidity rate of bronchial asthma has a complex causation that requires the search for informative methods for identification of causes and consequences of this dependence. Method for the assessment of the dependence of overall levels of morbidity rate of bronchial asthma on the degree of air pollution allows you to select a "useful information" of the direct impact of air pollution on a background of random processes and latent relationship between human and environment. The use of the method of the information entropy analysis allowed us to estimate the total and the individual contribution of the separate components of air pollution on the formation of levels of total morbidity rate of bronchial asthma in the population of the city of Vladivostok. Levels of total incidence of this pathology were established to differ in various age groups. The adult population is more adapted to air pollution, but retains a high sensitivity to the impact of nitrogen dioxide. Levels of overall l morbidity rate of bronchial asthma in children and adolescents depend on the total air pollution with some dominance of the influence of suspended matter and carbon monoxide.

[Antibiotic Resistance and Serotype Pattern of Streptococcus pneumoniae Isolated from Children in St. Petersburg in 2010-2013].

The surveillance of the serotype pattern and antibiotic resistance of S. pneumoniae in various geographical regions is required for the validity of rational etiotrophic therapy of pneumococcal infections and the choice of the optimal vaccines for their prophylaxis. 250 S. pneumoniae isolates from children with acute otitis or pneumonia and healthy carriers in St. Petersburg in 2010-2013 were investigated. The analysis of the serotype pattern of the pneumococci showed that 13-valent conjugate vaccine was the most active (86.1% of pneumococci causing pneumonia and 86.4% of pneumococci causing acute otitis). The isolates were higly resistant to beta-lactams and macrolides. By the EUCAST criteria, the decrease in the susceptibility to penicillin, cefotaxime, erythromycin and ceftarolin was observed in 32.4%, 14%, 33.2 and 6% of the isolates respectively. 22.4% of the isolates showed associate resistance to penicillin and erythromycin.. No resistance to moxifloxacin was detected. The frequency of resistance to tetracycline, co-trimoxasole and chloramphenicol in various patients ranged within 30-50%. The prevalence of the antibiotic resistance was mainly characteristic of the isolates serotypes 19A, 19F, 14 and serogroup 6.

The involvement of selected membrane transport mechanisms in the cellular uptake of (177)Lu-labeled bombesin, somatostatin and gastrin analogues.

INTRODUCTION: Radiolabeled receptor-targeting peptides are a useful tool for the diagnostic imaging and radiotherapy of some malignancies. However, the retention of radioactivity in the kidney may result in renal radiotoxic injury. This study seeks to evaluate the role of endocytic receptor megalin, renal SLC influx transporters and fluid phase endocytosis (FPE) in the cellular accumulation of radiolabeled peptides. METHODS: In vitro transport cellular studies using megalin ligands (RAP, albumin), fluid phase endocytosis (FPE) inhibitor rottlerin and low temperature were employed to evaluate the transport mechanisms of the peptides. Cells transfected with hOAT1 or hOCT2 were used to analyze the role of these SLC transporters. Somatostatin ((177)Lu-DOTA-[Tyr(3)]octreotate, (177)Lu-DOTA-[1-Nal(3)]octreotide), gastrin ((177)Lu-DOTA-sargastrin) and bombesin ((177)Lu-DOTA-[Pro(1),Tyr(4)]bombesin, (177)Lu-DOTA-[Lys(3)]bombesin, (177)Lu-PCTA-[Lys(3)]bombesin) analogues were involved in the study. RESULTS: RAP, albumin and low temperature decreased the accumulation of all the studied peptides significantly. With one exception, rottlerin caused the concentration dependent inhibition of the cellular accumulation of the radiopeptides. No significant differences in the uptake of the peptides between the control cells and those transfected with hOAT1 or hOCT2 were observed. CONCLUSION: The study showed that active transport mechanisms are decisive for the cellular accumulation in all tested (177)Lu-labeled somatostatin, gastrin and bombesin analogues. Besides receptor-mediated endocytosis by megalin, FPE participates significantly in the uptake. The tested types of renal SLC transporters are not involved in this process.

[Surgical treatment of lung metastases of kidney cancer].

The medical records of 60 patients who underwent surgery to remove the lung metastases of T1-4N0-2 kidney cancer were retrospectively analyzed. The age of patients ranged from 31 to 70 years. Synchronous lung metastases were diagnosed in 20 (33.3%) cases, metachronous - in 40 (66.7%). 53 (88.3%) patients had lesions in one lung, and 7 (11.7%) patients--in both lungs. Solitary metastases were present in 41 (68.3%) patients, multiple--in 19 (31.7%). In 69.4% of cases, the size of lung metastases was more than 2 cm. Metastasis at other sites at the time of surgery on the lungs were present in 1 patient (supraclavicular lymph nodes). The primary tumor was removed in 56 (93.3%) of 60 patients. All 60 patients underwent removal of lung metastases (radical--53 [88.3%]). One patient underwent a radical supraclavicular lymph node dissection. All tumor lesions were removed in 50 (83.3%) patients. Median followup period was 20 (3-155) months. Perioperative complication rate was 6.6%; no deaths caused by complications of treatment were registered. Histologically, metastases of renal cell carcinoma were verified in all removed lesions from the lungs; 3 (5%) patients had mediastinal lymph node metastases. Five- and 10-year overall, specific and recurrence free survival rates were 36.3 and 19.1%, 38.9% and 27.2, 20.4 and 11.7%, respectively. Univariate analysis demonstrated an adverse effect of pN + category, bilateral pulmonary lesions, the presence of mediastinal lymph nodes metastases and non-radical removal of malignant lesions of the lung on the specific survival. Multivariate analysis confirmed a significant effect of radical surgery on the survival.

Modulatory effects of quercetin and rutin on the activity, expression and inducibility of CYP1A1 in intestinal HCT-8 cells.

Flavonoids, plant secondary metabolites present in fruits and vegetables, show antioxidant and anti-tumorigenic effects in vitro, but their poor absorption from gastrointestinal tract limits their systemic efficacy in humans. On the other hand, flavonoids could protect intestinal cells against carcinogens by their potential to inhibit the enzymes metabolizing pre-carcinogenic compounds (e.g. CYP1A) to reactive ones. This work was designed to test the effect of quercetin (the most abundant flavonoid) and rutin (the most abundant glycosidic form) on the activity, expression and inducibility of CYP1A in intestinal HCT­8 cells. CYP1A enzymatic activity was measured by ethoxyresorufin-O-deethylase (EROD) activity, CYP1A protein expression was detected by western blotting. The effect of flavonoids on viability of cells was examined by neutral red uptake test. No cytotoxic effect of flavonoids up to 50 µM concentration was observed. Quercetin significantly inhibited EROD activity in the cells, where CYP1A had been preinduced by b-naphthoflavone and methylcholanthrene, and it also significantly reduced the CYP1A induction mediated by these model inducers. The effect of rutin was substantially weaker and mostly in significant in all conducted experiments. The results suggest that quercetin may have a potential to limit the CYP1A-mediated activation of pre-carcinogens in intestinal cells.

[The criteria of differentiated diagnostics of early arthritis on the basis of analysis of serum hyaluronidase and deoxyribonuclease activity].

The study analyzed serum hyaluronidase and deoxyribonuclease activity in patients with early arthritis--early rheumatoid arthritis and acute reactive arthritis. The criteria of their differential diagnostics were developed on the basis of data obtained. The genuine methods were applied to analyze hyaluronidase and deoxyribonuclease activity of blood serum based on formation of clot of etacridine acetate (rivanol) with hyaluronic acid and DNA inversely proportionally to their polymerization under the impact of enzymes. The increased serum hyaluronidase and deoxyribonuclease activity was established in patients with early arthritis as compared with control group (p < 0.001). The prevalence of mentioned types of activity under early rheumatoid arthritis as compared with acute reactive arthritis was detected too. The rests for differentiate diagnostics of early rheumatoid arthritis and acute reactive arthritis were developed conformed to criteria of the most useful diagnostic tests in rheumatology.

[Alteration of VHL gene in patients with metastatic renal cell carcinoma].

Blocks of preparations from 22 patients with metastatic renal cell carcinoma on target therapy were studied. The patients were examined for mutations/methylation of VHL gene. The mutations were detected in 10 (45.5%) of 22 patients, VHL methylation was found in 1 (4.5%) patient. Overall survival was 36.4 and 66.7% in the groups of patients with and without gene VHL alteration, respectively. Progression-free survival was 47.6 and 57.1%, respectively (p = 0.619), relapse-free survival--63.6 and 45.5%, respectively (p = 0.682), progression was registered in 36.4 and 54.5%, respectively (p = 0.682). Gene VHL inactivation had no effect on prognosis of the disease and results of anti-angiogenic therapy.

[Interdisciplinry approach to the treatment of diffuse germinogenic ovarian tumours].

The first stage in the treatment of disseminated germinogenic ovarian tumours (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group. Dynamic observation is indicated in case of incomplete induction in patients with seminoma excepting those with PET-positive residual tumours bigger than 3 cm to whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated. Ablation of residual tumour of any localization is indicated to patients with disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of tumour markers. The necessity of adjuvant chemotherapy in case of a viable malignant HOT in the removed tissues remains debatable. Refractory and recurring HOT are usually treated with a combination of fosfamide and vinblastine. Residual tumours need to be removed after salvation chemotherapy. Surgical treatment is the preferred option for the management of late NHOT relapses.

[Retroperitoneal lymphadenectomy in disseminated non-seminoma germinogenic testicular tumors after chemotherapy in patients with elevated serum tumor markers].

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

[Results of surgical and radiotherapy of prostatic cancer T1-4N0-1M0].

To compare the results of radical prostatectomy and conformal radiotherapy in prostatic cancer T1-4N0-1M0, we made a retrospective study of 306 patients with prostatic cancer T1-4N0-1M0 of whom 144 (47.1%) were treated surgically (radical prostatectomy) while 162 (52.9%) were exposed to extracorporeal conformic radiotherapy. Follow-up median was 30.7 +/- 29.8 months. Five and 10-year overall, specific and PSA recurrence free survival in 306 patients was 94.0% and 90.1% (median was not achieved), 96.6% and 94.3% (median was not achieved), 66.1 and 49.2% (median was 84.0 +/- 4.4 months). In multifactorial analysis significant prognostic factors of PSA recurrence free survival were T category (p = 0.021) and Glison's sum (p = 0.002). In the subgroup of patients with local prostatic cancer there was a significant superiority of the operated patients by PSA recurrence free survival over irradiated group in baseline PSA < 10 ng/ ml (p = 0.015), Glison's index < 7 (p = 0.071) and combination of these factors (p = 0.018). A favourable prognosis factor of PSA recurrence free survival in operated patients was operative Glison's index < 7 (p = 0.001), among operated patients--nadir PSA < 1 ng/ ml (p = 0.003). Surgical and radiation treatment of local and locally advanced prostatic cancer provided satisfactory results. In the group of good prognosis (cT1-2N0, PSA < 10 ng/ml, Glison's sum < 7) radical prostatectomy gives advantage of PSA recurrence free survival. In patients with prostatic cancer cT > T2, N+, Glison's index > 7 and PSA > 10 ng/ml surgical treatment and remote radiotherapy are equally effective in respect to survival free of biochemical recurrence.

[Prognostic implications of preoperative diagnosis of clinically local and locally advanced prostatic cancer].

The data of preoperative diagnosis and morphological examination were compared for 144 patients with prostatic carcinoma T1-4N0-XM0 subjected to radical prostatectomy in 1997-2007. In assessment of prostatic capsule invasion, sensitivity of the rectal examination was 21.7%, specificity--89.8%, diagnostic efficacy--68.1%, PPV--50.0%, NPV--70.9%, AUC under ROC curve--0.558 +/- 0.053 (p = 0.348); sensitivity of transrectal ultrasonic investigation--21.7%, specificity--89.8%, diagnostic efficacy--68.8%, PPV--52.6%, NPV--71.2%, AUC under ROC curve--0.563 +/- 0.053 (p = 0.211). Factors of a poor prognosis of prostatic capsule invasion were PSA > 10 ng/ml (p = 0.028) and Gleason score > 7 (p = 0.052). Combined use of these two parameters raises quality of preoperative assessment of category T [sensitivity--80.0%, specificity--55.1%, diagnostic efficacy--56.3%, PPV--80.4%, NPV--44.9%, AUC under ROC curve--0.624 +/- 0.049 (p = 0.017)]. Sensitivity of clinical assessment of N category was 11.1% in 100% specificity, 94.4% diagnostic efficacy, 100% PPV, 94.4% NPV, 0.556 +/- 0.107 (p = 0.577) AUC under ROC curve. A single significant prognostic factor of pN+ category was PSA > 10 ng/ml (p = 0.014). Sensitivity of histological examination of biopsy material in relation to true Gleason's parameter (< 7 or > 7) was 59.4%, specificity 89.3%, diagnostic efficacy 82.6%, PPV 61.3%, NPV 88.5%, AUC under ROC curve 0.743 +/- 0.056 (p < 0.0001). Thus, combined use of a baseline PSA concentration with a borderline value > 10 ng/ml and biopsy Gleason score > 7 raises quality of preoperative evaluation of extraprostatic tumor extension and condition of regional lymph nodes.

[Cerebrovascular serotonin antagonists and agonist among tropan derivatives].

A series of new tropan derivatives have been synthesized and investigated, which can both weaken and potentiate the serotonin-induced cerebrovascular constrictory reactions. The compound LK-728 produces a pronounced antiserotonin cerebrovascular action comparable to that of tropoxin, but being superior to the reference drug in the effect duration. On the contrary, another tropan derivative LK-769 enhances the cerebrovascular response to serotonin. A similar effect was demonstrated with the well-known antimigraine agent sumatriptan, which is an agonist of 5HT1B/1D receptors. The ability of sumatriptan to increase the local cerebral blood flow which was observed in our experiments, may also play an important role in the mechanism of the antimigraine action produced by this serotonin receptor agonist.