Search

Lipophilicity was investigated for 20 2'-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D 7.4 ) for ionic compounds were determined as a lipophilicity descriptor using a shake-flask method. All modified nucleosides had P/D 7.4 values higher than those of an appropriate unmodified 2'-closo-dodecaborane and metallacarborane was found to be three orders of magnitude higher than that of its unmodified counterpart. The lowest impact on the P/D 7.4 values of the conjugates was observed for the 7,8-dicarba-nido-undecaborate anion. A preliminary molecular modeling study of a thymidine-carborane conjugate with β-cyclodextrin confirmed the ability of the components to form an inclusion complex., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To evaluate if there are differences in toxicity and efficacy between different Bacillus Calmette-Guerin (BCG) stains used for intravesical immunotherapy in patients with non-muscle invasive bladder cancer., Methods: We retrospectively analysed a group of 844 patients who received TICE, RIVM and Moreau BCG strains. The allocation of the strain to each patient was random, stemming from differences in supply and distribution. The patients were analysed in terms of toxicity, recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS) and overall survival (OS)., Results: In the survival analysis, statistical significance was not reached in any tumour group for any clinical event. TICE caused more local and mild adverse effects and severe complications were mainly associated with RIVM strain. In a group in which the strain was changed during the course of the therapy, significantly more severe complications were observed and, in most of these cases, complications appeared right after the strain change., Conclusions: There were no differences in terms of RFS, PFS, CSS and OS after use of TICE, RIVM and Moreau strains. The complication profile differed statistically between used strains with TICE causing mostly mild complications. Also, strain change during the therapy course was associated with the increased risk of moderate to severe toxicity occurrence., (© 2018 S. Karger AG, Basel.)

Idiopathic overactive bladder due to its high impact on quality of life and high prevalence is a significant problem in everyday clinical practice. Currently, we do not have medicines that allow patients to be cured completely. Therapy is focused on the elimination or reduction of symptoms. An established position in the treatment of this disease for many years has a botulinum toxin. This therapy is used in patients whose conservative methods have not improved or are not acceptable because of side effects. The therapeutic effect after the injection of bladder detrusor muscle is limited in time and does not occur in all patients. Patients who benefit from this therapy require repeated procedures to reduce the symptoms of the disease. Many authors modify the standard treatment protocol of botulinum toxin in idiopathic overactive bladder in search of better results. The main goal is to improve the efficiency and extend the duration of the drug while reducing side effects. Undoubtedly, the technique of botulinum toxin injection has an effect on the final effect of treatment. The location and depth of punctures, the dose of the drug, preparation of the drug solution, periprocedural management and prophylaxis, and observation of the patient after the procedure are some issues whose modifications in the literature have been studied in order to achieve additional benefits from this therapy. In our work, we discuss the technical and practical aspects of this procedure in the search for the most optimal treatment protocol with the use of botulinum toxin in the treatment of idiopathic overactive bladder.

Introduction: Great advances in medical research concerning methods of contraception have been achieved in recent years, however, more than 25% of couples worldwide still rely on condoms - a method with poor efficacy. Even though there is a spectrum of 11 different contraceptive methods for women, there are only 4 commonly used by men (condoms, periodic abstinence, withdrawal and vasectomy). In this review, advances and present, state-of-the-art, both hormonal and non-hormonal male contraceptive methods will be presented and evaluated. Potential novel targets that warrant greater research will be highlighted., Material and Methods: A comprehensive literature search without a time limit was performed using the Medline database on May 2017. The terms 'male contraception' in conjunction with 'reversible inhibition of sperm under guidance' (RISUG), 'hormonal', 'non-hormonal', 'vasectomy' or 'testosterone' were used. The articles were limited to those published in English, Polish or French., Results: There are various contraceptives currently available to regulate male fertility. Vasectomy is still the most effective permanent form of male contraceptive with a failure rate lower than 1%. Reversible, non hormonal methods of male contraception, like reversible inhibition of sperm under guidance, are very promising and close to being introduced into the market. In regards to hormonal contraception research, the use of testosterone injections has been widely studied yet they often harbor undesirable side effects and require further development., Conclusions: Despite continuous efforts worldwide, it seems that another several years of research is needed to provide safe, effective and affordable male contraceptives which will allow both men and women to participate fully in family planning.

Objectives: Cancer is one of the main cause of death in Western countries. Inflammation plays an important role in the pathogenesis of cancer. Nicotinamide (NA) - known for its anti-inflammatory properties - participates in the processes related to the cell cycle regulation and DNA repair, which are relevant in cancer development. This study aimed to investigate the nicotinamide metabolism alterations in bladder cancer., Methods: Blood and plasma samples of patients with bladder cancer were collected. Blood pyridine and adenine nucleotides concentration were measured using high performance liquid chromatography (HPLC). Plasma nicotinamide metabolites concentration were determined using high performance liquid chromatography - mass spectrometry (LC/MS)., Results: Our results indicated that the development of bladder cancer caused significant decrease in the concentration of N-methylnicotinamide (MetNA) (0.07 ± 0.02 vs 0.1 ± 0.03 µmol/l) and an increase in the concentration of N-methyl-2-pyridone-5-carboxamide (Met2PY) - one of the final nicotinamide metabolites: (1.1 ± 0.15 vs 0.7 ± 0.07 µmol/l) in comparison to the control. The association between the stage of cancer and the increase in both, Met2PY and Met4PY levels was observed. Blood ATP and NAD levels were significantly decreased in bladder cancer patients as compared to the control (970.8 ± 77.84 vs 1165.00 ± 57.76 µmol/l; 45.86 ± 2.98 vs 53.06 ± 2.28 µmol/l respectively)., Conclusions: Bladder cancer development caused substantial changes in nicotinamide metabolism, such as decreased plasma MetNA and increased Met2PY concentration. Analysis of the nicotinamide and its metabolites concentrations - as new biomarkers - may allow to track the course of pathological processes in cancer.

Objective: The aim of this study was to test the addition of methylene blue (MB) to onabotulinum toxin A (BTX-A) solution in overactive bladder (OAB) treatment, as a means of facilitating observation of the injection site and assessing the distribution of the drug under the bladder mucosa during injection. Pharmacological interactions between BTX-A and MB were also evaluated., Materials and Methods: The study was conducted between December 2014 and April 2016 on 30 patients: six males and 24 females (median age 57.7, range 23-80 years) diagnosed with OAB, who qualified for intravesical BTX-A injection. Each received 100 IU of BTX-A (Botox ® ; Allergan), dissolved in 9.5 ml of 0.9% NaCl with the addition of 0.5 ml of MB. Cystoscopy with submucosal injection of the solution was performed systematically, including the bladder triangle. For pharmacological evaluation, quantitative determination of MB was performed on a capillary electrophoresis system with diode array detection., Results: In the course of 600 injections, the addition of MB facilitated the observation of the procedure; the exact distribution of the solution could not be observed in only 43 injections in seven patients. The range of distribution of the drug varied from 1 to 2.5 cm. Pharmacological evaluation based on visual observations and experiments showed that pharmaceutical interactions do not occur between MB and this commercially available formulation of BTX-A., Conclusions: Applying a coloured solution of BTX-A significantly facilitates observation of the procedure and assessment of drug distribution. There are no pharmaceutical interactions between MB and BTX-A.

Objectives: To preclinically evaluate drug-eluting biopsy needles (patent pending WO2016118026) as a new potential way of antimicrobial prophylaxis for transrectal prostate biopsy., Methods: Twenty steel biopsy needles have been coated with polyvinyl alcohol, ciprofloxacin, and amikacin. Modified biopsy needles have been randomly divided into 3 groups (1:2:1 ratio). Needles from group I were immersed for 30 minutes in dedicated test tubes containing saline. Needles from group II were immersed (one by one) for 5 seconds in a set of 12 test tubes containing saline. Then, each solution was analyzed using high-performance liquid chromatography. The results were compared with the susceptibility break points for Escherichia coli . Group III was incubated with E coli strains on Mueller-Hinton plate and then the bacterial inhibition zones surrounding needles were measured., Results: The average concentration of antibiotics eluted from needles (group I) was 361.98 ± 15.36 µg/mL for amikacin and 63.87 ± 5.95 µg/mL for ciprofloxacin. The chromatographic analysis revealed the gradual release of both antibiotics from needles (group II). The concentration of amikacin released from needles exceeded the break-point value from first to ninth immersion. Ciprofloxacin concentration was higher than break-point value in all immersions. The average bacterial inhibition zone minor axis was 42 ± 5.7 mm (group III)., Conclusions: The use of drug-eluting biopsy needle could be a new potential way of antimicrobial prophylaxis for transrectal prostate biopsy. This study confirmed its biological activity as well as the gradual release of antibiotics from its surface. Confirmation of its preventive role, in terms of infectious complications after transrectal prostate biopsy, has to be evaluated in a clinical trial.

Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the intrahost immune response to influenza virus infection. The model is fit to experimental data for young and old mice infected with influenza virus. We generated distinct sets of rules for each age group to capture the temporal differences seen in the immune responses of these mice. These rules describe a network of interactions leading to either clearance of the virus or death of the host, depending on the initial dosage of the virus. Our models clearly demonstrate differences in these two age groups, particularly in the innate immune responses., (Copyright © 2017 American Society for Microbiology.)

INTRODUCTION Massive consumption of dietary supplements, including vitamins and minerals, has recently become a serious health issue in Europe. Their use may negatively affect the pharmacological activity of various medications, including antiallergic drugs. Calcium preparations are commonly used in some European countries as a popular remedy for allergy‑related skin reactions, such as itching, erythema, and wheals, as well as insect bites. However, so far there have been no reliable studies to prove their action.  OBJECTIVES The aim of this randomized, double‑blind, placebo‑controlled study was to investigate the efficacy of calcium salts in allergic reactions, using an allergen‑induced skin prick test (SPT).  PATIENTS AND METHODS Forty adult volunteers with allergic rhinoconjunctivitis or asthma (or both) were recruited to receive oral calcium carbonate (1000 mg) or placebo 3 times a day for 3 days. SPTs were performed with 11 aeroallergen extracts at baseline and at 4 and 72 hours after drug administration. The wheal diameter was measured. We also used the visual analog scale to evaluate the intensity of pruritus. RESULTS There was no difference in the wheal size or pruritus between patients receiving calcium or placebo at any of the time points (P >0.05). Calcium preparations were well tolerated.  CONCLUSIONS We found no evidence to support the efficacy of calcium preparations in allergy‑related skin reactions associated with itching and wheals. Calcium preparations do not suppress SPT responses; moreover, their use in allergic patients should be discouraged due to their possible interference with the absorption of antiallergic drugs.

We demonstrate the existence of a novel quasiparticle, an exciton in a semiconductor doubly dressed with two photons of different wavelengths: a near infrared cavity photon and terahertz (THz) photon, with the THz coupling strength approaching the ultrastrong coupling regime. This quasiparticle is composed of three different bosons, being a mixture of a matter-light quasiparticle. Our observations are confirmed by a detailed theoretical analysis, treating quantum mechanically all three bosonic fields. The doubly dressed quasiparticles retain the bosonic nature of their constituents, but their internal quantum structure strongly depends on the intensity of the applied terahertz field.

A t 6 A nucleoside was efficiently and stereospecifically transformed into a hydantoin cyclic form of N 6 -l-threonylcarbamoyladenosine (ct 6 A) by the use of polymer bounded carbodiimide (EDC-P) and HOBt. The procedure was successfully applied for a post-synthetic conversion of t 6 A-containing RNA 17-mers (of the sequences of anticodon stem and loop (ASL) fragments of S. pombe tRNA i and E. coli tRNA Lys ) into the products bearing the ct 6 A unit.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70-80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo pathway and acts as a transcriptional co-activator of genes involved in the processes of growth and development of tissues. Hippo signaling, with its key kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant role in the negative regulation of the amount and activity of YAP1 protein. Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a variety of tumors, suggestive of their possible involvement in carcinogenesis. Our aim was to evaluate gene and protein expression profiles of YAP1, MST2 and LATS1 and the methylation status of MST2 and LATS1 promoters in ccRCC. mRNA levels of MST2, LATS1 and YAP1 genes were assessed in the tumor and matched normal kidney tissues of 86 patients, and in 12 samples of local metastases by quantitative PCR (qPCR). Proteins were semi-quantified in 58 patient samples by western blotting. Hypermethylation of LATS1 and MST2 promoters was measured by methylation‑specific high‑resolution-melting qPCR. We found that LATS1 promoter hypermethylation, decreased LATS1 mRNA/protein and increased YAP1 mRNA/protein levels in tumor samples were associated with higher TNM and Fuhrman's stages and patient survival. Higher YAP1 mRNA levels were associated with poor outcome (HR=4.03, p=0.036). No changes in MST2 (promoter/mRNA/protein) were found. We propose that deregulation of LATS1 and YAP1 expression is associated with ccRCC progression and poor patient survival. Measurement of YAP1 mRNA levels in paired tumor-normal kidney tissue samples may serve as a new prognostic factor in ccRCC.

Introduction: The aim of the study was to compare 2 methods of the sentinel lymph node biopsy (SLNB) procedure in bladder cancer: we applied technetium radiocolloid (RadCol) detected by a gamma ray detection probe, and indocyanine green (ICG) detected by a near-infrared fluorescent (NIRF) camera., Material and Methods: The SLNB was performed on 50 patients using the RadCol and the ICG, followed by a lymphadenectomy and a pathologic examination., Results: In the analyzed group of 47 patients (3 patients were excluded owing to the lack of lymphatic drainage from the tumor), the SLNB was performed using the 2 methods. The ICG with a NIRF-guided camera detected all sentinel lymph nodes (SLNs) in 46 cases, whereas RadCol detected them in 45 cases. In 12 (25.6%) of 47 patients, the ICG-fluorescent method revealed more SLNs than the RadCol method. In 8 (17%) patients, the SLNs revealed in the ICG fluorescence were metastatic. In 3 (6.4%) patients, we found SLNs outside the standard lymphadenectomy template, but a histopathologic examination showed they were negative for cancer. In 3 (6.4%) patients, the SLNs detected by both methods were negative for cancer, but other resected lymph nodes revealed metastases., Conclusion: Our study shows that SLNB procedure with the RadCol or the ICG method is useful for the evaluation of lymph nodes in bladder cancer. The new ICG fluorescent technique with a NIRF camera system is safe, enables live view of the results of the procedure, and does not create additional costs. However, it highlights more lymph nodes than the radioactive method., (Copyright © 2016 Elsevier Inc. All rights reserved.)

N6-Threonylcarbamoyladenosine (t6A) and its derivatives are universally conserved modified nucleosides found at position 37, 3΄ adjacent to the anticodon in tRNAs responsible for ANN codons. These modifications have pleiotropic functions of tRNAs in decoding and protein synthesis. In certain species of bacteria, fungi, plants and protists, t6A is further modified to the cyclic t6A (ct6A) via dehydration catalyzed by TcdA. This additional modification is involved in efficient decoding of tRNALys. Previous work indicated that the chemical structure of ct6A is a cyclic active ester with an oxazolone ring. In this study, we solved the crystal structure of chemically synthesized ct6A nucleoside. Unexpectedly, we found that the ct6A adopted a hydantoin isoform rather than an oxazolone isoform, and further showed that the hydantoin isoform of ct6A was actually present in Escherichia coli tRNAs. In addition, we observed that hydantoin ct6A is susceptible to epimerization under mild alkaline conditions, warning us to avoid conventional deacylation of tRNAs. A hallmark structural feature of this isoform is the twisted arrangement of the hydantoin and adenine rings. Functional roles of ct6A37 in tRNAs should be reconsidered., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Transfer RNA modifications play pivotal roles in protein synthesis. N6-threonylcarbamoyladenosine (t6A) and its derivatives are modifications found at position 37, 3΄-adjacent to the anticodon, in tRNAs responsible for ANN codons. These modifications are universally conserved in all domains of life. t6A and its derivatives have pleiotropic functions in protein synthesis including aminoacylation, decoding and translocation. We previously discovered a cyclic form of t6A (ct6A) as a chemically labile derivative of t6A in tRNAs from bacteria, fungi, plants and protists. Here, we report 2-methylthio cyclic t6A (ms2ct6A), a novel derivative of ct6A found in tRNAs from Bacillus subtilis, plants and Trypanosoma brucei. In B. subtilis and T. brucei, ms2ct6A disappeared and remained to be ms2t6A and ct6A by depletion of tcdA and mtaB homologs, respectively, demonstrating that TcdA and MtaB are responsible for biogenesis of ms2ct6A., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Fluoroquinolones are the drugs of choice in the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. In order to improve assessment of antibacterial efficacy in the target tissue a simple, selective, rapid and robust HPLC-ESI-MS/MS method for the determination of levofloxacin and ciprofloxacin concentrations in human prostate bioptates was developed and validated. Preparation procedure for prostate samples (10mg) was carried out using homogenization and filtration steps. Analyses were performed within 3.5min using RP C 18 column in the isocratic elution mode with mobile phase composed of a mixture of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution (v/v; 79:21). The method was linear between 0.3μg/g and 15μg/g for levofloxacin and ciprofloxacin with coefficient of correlation (r) ≥0.999. The limit of detection and the limit of quantification for levofloxacin were 0.06μg/g and 0.2μg/g and for ciprofloxacin were 0.04μg/g and 0.13μg/g, respectively. Average concentrations (±SD) of levofloxacin and ciprofloxacin obtained from patients tissue were 5.4±2.2μg/g and 3.9±1.5μg/g, respectively. Additionally, during validation procedure a novel, experimental design approach was applied for the robustness study. For evaluation of analytical method robustness, Plackett-Burman design was employed and for sample preparation method robustness Fractional Factorial design was used. The developed and validated method was successfully applied to examine prostate tissue samples obtained from patients enrolled into a clinical study. Up to now, there has been no other HPLC-ESI-MS/MS method reported for the simultaneous determination of levofloxacin and ciprofloxacin in human prostatic tissue., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Invasion and migration of cancer cells are crucial for the formation of secondary lesions. These require activation of signalling cascades modulated by the number of regulatory molecules. One such molecule is CD151, a member of evolutionary conserved tetraspanin family. CD151 is involved in cell adhesion, motility and cancer progression due to formation of complexes with laminin-binding integrins and regulation of growth factor receptors function (e.g. HGFR, TGFβR, EGFR). Recent studies point to correlation between CD151 expression and high tumour grade in prostate cancer (PCa). Herein, we investigated a possible role of CD151 in communication between PC3 cancer cells and either cancer-associated fibroblasts (CAFs) or osteoblasts, an interplay which is significant for metastasis. The analysis showed that although CAFs strongly enhanced both migration and invasion of PC3 prostate cancer cells, the effect was not dependent on CD151. On the other hand, CD151 was found to promote 3D migration as well as invasive growth in response to osteoblasts-secreted growth factors. Obtained data revealed that knockdown of CD151 abolished activation of pro-migratory/pro-survival kinases (i.e FAK, Src, HSP27) triggered by osteoblasts, along with expression of matrix metalloproteinase-13. This suggests that CD151 participates in communication between PC3 cells and bone microenvironment and the process can be considered as a significant step of PCa progression and metastasis.

Background/aims: This study investigated the gene expression and DNA methylation of selected DNA repair genes (MBD4, TDG, MLH1, MLH3) and DNMT1 in human bladder cancer in the context of pathophysiological and prognostic significance., Methods: To determine the relationship between the gene expression pattern, global methylation and promoter methylation status, we performed real-time PCR to quantify the mRNA of selected genes in 50 samples of bladder cancer and adjacent non-cancerous tissue. The methylation status was analyzed by methylation-specific polymerase chain reaction (MSP) or digestion of genomic DNA with a methylation-sensitive restriction enzyme and PCR with gene-specific primers (MSRE-PCR). The global DNA methylation level was measured using the antibody-based 5-mC detection method., Results: The relative levels of mRNA for MBD4, MLH3, and MLH1 were decreased in 28% (14/50), 34% (17/50) and 36% (18/50) of tumor samples, respectively. The MBD4 mRNA expression was decreased in 46% of non-muscle invasive tumors (Ta/T1) compared with 11% found in muscle invasive tumors (T2-T4) (P<0.003). Analysis of mRNA expression for TDG did not show any significant differences between Ta/T1 and T2-T4 tumors. The frequency of increased DNMT1 mRNA expression was higher in T2-T4 (52%) comparing to Ta/T1 (16%). The overall methylation rates in tumor tissue were 18% for MBD4, 25% for MLH1 and there was no evidence of MLH3 promoter methylation. High grade tumors had significantly lower levels of global DNA methylation (P=0.04). There was a significant association between shorter survival and increased expression of DNMT1 mRNA (P=0.002), decreased expression of MLH1 mRNA (P=0.032) and the presence of MLH1 promoter methylation (P=0.006)., Conclusion: This study highlights the importance of DNA repair pathways and provides the first evidence of the role of MBD4 and MLH3 in bladder cancer. In addition, our findings suggest that DNMT1 mRNA and MLH1 mRNA expression, as well as the status of MLH1 promoter methylation, are attractive prognostic markers in this pathology., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Fluoroquinolones are considered as gold standard for the prevention of bacterial infections after transrectal ultrasound guided prostate biopsy. However, recent studies reported that fluoroquinolone- resistant bacterial strains are responsible for gradually increasing number of infections after transrectal prostate biopsy. In daily clinical practice, antibacterial efficacy is evaluated only in vitro, by measuring the reaction of bacteria with an antimicrobial agent in culture media (i.e. calculation of minimal inhibitory concentration). Such approach, however, has no relation to the treated tissue characteristics and might be highly misleading. Thus, the objective of this study was to develop, with the use of Design of Experiments approach, a reliable, specific and sensitive ultra-high performance liquid chromatography- diode array detection method for the quantitative analysis of levofloxacin in plasma and prostate tissue samples obtained from patients undergoing prostate biopsy. Moreover, correlation study between concentrations observed in plasma samples vs prostatic tissue samples was performed, resulting in better understanding, evaluation and optimization of the fluoroquinolone-based antimicrobial prophylaxis during transrectal ultrasound guided prostate biopsy. Box-Behnken design was employed to optimize chromatographic conditions of the isocratic elution program in order to obtain desirable retention time, peak symmetry and resolution of levofloxacine and ciprofloxacine (internal standard) peaks. Fractional Factorial design 2(4-1) with four center points was used for screening of significant factors affecting levofloxacin extraction from the prostatic tissue. Due to the limited number of tissue samples the prostatic sample preparation procedure was further optimized using Central Composite design. Design of Experiments approach was also utilized for evaluation of parameter robustness. The method was found linear over the range of 0.030-10μg/mL for human plasma and 0.300-30μg/g for human prostate tissue samples. The intra-day and inter-day variability for levofloxacine from both plasma and prostate samples were less than 10%, with accuracies between 93 and 108% of the nominal values. The limit of detection and the limit of quantification for human plasma were 0.01μg/mL and 0.03μg/mL, respectively. For the prostate tissue, the limit of detection and the limit of quantification were 0.1μg/g and 0.3μg/g, respectively. The average recoveries of levofloxacin were in the range from 99 to 106%. Also, the method fulfills requirements of robustness what was determined and proved by Design of Experiments. The developed method was successfully applied to examine prostate tissue and plasma samples from 140 hospitalized patients enrolled into the clinical study, 12h after oral administration of LVF at a dose of 500mg. The mean (±SD) LVF concentration in prostate was 6.22±3.52μg/g and in plasma 2.54±1.14μg/mL. Due to simplicity of the method and relative small amount of sample needed for the assay, the method can be applied in clinical practice for monitoring of LVF concentrations in plasma and prostate gland., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: Lymph outflow from bladder tumor differs between individuals, making the prediction of the metastatic landing sites difficult. A "blind" template of lymphadenectomy has been tested as a solution to this problem. We believe that it is feasible to find methods enabling more precise lymph nodes (LNs) evaluation. The aims of our study were to evaluate the possibility of LNs mapping in case of muscle invasive bladder cancer (MIBC) and to compare the 2 methods of their detection., Patients and Methods: Our study group consisted of 38 cN0 MIBC patients. Lymph nodes mapping was performed by SPECT/CT lymphoscintigraphy using Tc-nanocolloid, followed by intraoperative verification with γ-ray probe. Lymph nodes with increased radiotracer uptake (hot spots) were removed, and then pelvic LNs dissection was conducted. Lymph nodes resected as hot spots and LNs resected with lymphadenectomy were separately examined by a pathologist., Results: An average of 3 hot spots (range, 1-5) were identified in each case. For 36 of 38 patients, both preoperative SPECT/CT and intraoperative γ-probe evaluation results were obtained. Ninety-five percent of hot spots were found distally and caudally to the uretero-iliac crossing; 5% were found proximal. Lymph nodes outside the pelvic LNs dissection area did not contain metastases. In 2 patients, metastases were found in LNs without increased radiotracer uptake, and the observed hot spots contained no metastases., Conclusions: Radio-guided LNs mapping in case of MIBC is feasible. Preoperative detection of hot spots using SPECT/CT and intraoperative γ-ray detection probe gives similar results.

Introduction: Cystourethroscopy (CS) is an endoscopic method used to visualize the urethra and the bladder., Aim: In this study, we prospectively evaluated pain in men undergoing cyclic cystoscopic assessment with rigid and flexible instruments after transurethral resection of bladder tumor (TURB)., Material and Methods: One hundred and twenty male patients who were under surveillance after a TURB procedure due to urothelial cell carcinoma and who had undergone at least one rigid cystourethroscopy in the past were enrolled in the trial. Patients were prospectively randomized to age-matched groups for flexible (group F) or rigid (group R) CS. Patient's comfort was evaluated on an 11-grade scale, ranging from 0 (free from pain) to 10 points (unbearable pain)., Results: The patients described the pain during the previous rigid CS as ranging from 4 to 10 (mean: 6.8) in group F and from 0 to 10 (mean: 5.8) in group R. Group R patients described the pain during the current rigid CS as ranging from 0 to 10 (mean: 5.7). No mean change in the grade was observed between the two pain descriptions (no change 11 patients, weaker pain 25 patients, stronger pain 24 patients, gamma 0.51, p < 0.0001). Group F described the pain as 1 to 5 (mean: 2.1). In the case of flexible CS the pain experience was greatly lowered compared to the previous rigid CS. All flexible CS patients reported lowered pain (by 1 to 9 grades). Patients' age did not influence the comfort of the flexible CS or the change in pain level., Conclusions: Flexible CS is better tolerated than rigid cystoscopy by male patients regardless of patients' age.

Objective: Sunitinib is a multiple tyrosine kinase inhibitor (TKI) that exerts anti-tumor and antiangiogenic activity. It is used for the treatment of metastatic gastrointestinal stromal tumours, renal cell carcinoma and pancreatic neuroendocrine tumours. A few studies confirm the anti-tumour activity of sunitinib in brain tumours and uveal melanoma, as well as its efficacy in the reduction of brain metastases of some primary cancers. Therefore, the penetration of sunitinib through the blood-brain barrier (BBB) and blood-aqueous humour barrier (BAB) is an issue of growing interest. The aim of the study was to investigate the influence of the time-of-day administration on the penetration of sunitinib into the cerebrospinal fluid (CSF) and aqueous humour (AH)., Materials and Methods: The rabbits were divided into two groups: I (control group)--receiving sunitinib at 8 a.m., and II--receiving sunitinib at 8 p.m. Sunitinib was administered p.o. at a single dose of 25 mg. The concentrations of sunitinib and its active metabolite (SU12662) in the plasma, CSF, AH were measured with the validated HPLC-UV method., Results: The plasma AUC0-t for sunitinib in group I was 2051.8 ng × h/mL, whereas in group II it was 3069.3 ng × h/mL. The aqueous humour AUC0-t for sunitinib in thr groups were 43.2 and 76.3 ng × h/mL, respectively. The cerebrospinal AUC0-t for sunitinib in groups I and II were 55.5 and 66.3 ng × h/mL, respectively., Conclusions: After the evening administration (8 p.m.) the exposure to sunitinib in the rabbits' plasma, AH and CSF was higher than after the morning administration (8 a.m.), but the degree of sunitinib penetration through the BAB and BBB was very low (< 5%) and comparable in both groups.

Introduction: Urological complications after renal transplantation occur in between 2.5% and 30% of all graft recipients. The aim of the study was to present 7 years of experience in urological treatment of patients with a transplanted kidney. We aimed to identify retrospectively late urological complications in renal transplant recipients at a single center and analyze the treatment modalities and their outcome., Material and Methods: Between January 2008 and December 2014, a total of 58 patients after KTX were treated in the Department of Urology because of post-transplant urological complications that occurred during follow-up at the Transplant Outpatient Department. Retrieved data were analysed in retrospectively., Results: In the group of 38 patients with ureteral stenosis (Clavien grade III), 29 patients underwent endoscopy, 8 open surgical procedures and one both endoscopic and open operation. Ten patients were admitted with symptomatic lymphocoele (Clavien III), of which 9 were successfully treated with drainage and one with surgical marsupialization. Because of urolithiasis in the grafted kidney (Clavien grade III), 4 patients were treated with ureterorenoscopic lithotripsy (URSL) and one only with the extracorporeal shock wave lithotripsy (ESWL) procedure. Five urethral strictures plasties and one graftectomy because of purulent pyelonephritis were also conducted. The average age in the group of recipients who experienced urologic complications was similar (46.1 vs. 47.8) to those without complications. There was no vesicoureteral reflux or ureteral necrosis requiring surgical intervention, no graft loss and death related to urological complication and treatment., Conclusions: Most complications could be successfully treated with endourological procedures. The kidney function improved in the majority of patients., Competing Interests: The authors declare no conflicts of interest.

Clear-cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70-80%) and is associated with poor prognosis in 40% of cases mainly due to metastasis in the course of the disease. RASSF1, with its isoforms RASSF1A and RASSF1C, is a tumor suppressor gene which has not been fully analyzed in ccRCC yet. The epigenetic downregulation of RASSF1A is commonly associated with promoter hypermethylation. The aim of the present study was to compare the ccRCC outcomes with the expression of RASSF1A and RASSF1C. Tissues were obtained from 86 ccRCC patients. RASSF1A and RASSF1C mRNA levels were assessed in tumor and matched normal kidney tissue, and in 12 samples of local metastases by quantitative PCR (qPCR). RASSF1A and RASSF1C proteins levels were semi-quantified in 58 samples by western blot analysis and their tissue localization was assessed by immunohistochemistry. Hypermethylation of RASSF1A promoter was measured by high-resolution-melting methylation-specific qPCR. RASSF1A mRNA levels were 4 and 5 times lower in 66% of tumor and 75% metastasized samples. RASSF1A hypermethylation was found in 40% of analyzed T cases. RASSF1A protein expression was 5 or 20 times decreased in 70% tumor and 75% metastatic samples, respectively. RASSF1A hypermethylation, mRNA and protein levels were associated with TNM progression and higher Fuhrman's grading. Decreased RASSF1A expression, hypermethylation, TNM and Fuhrman's grading were associated with poorer overall survival (OS). Cox hazard ratio (HR) analysis revealed predictor role of RASSF1A mRNA levels on OS and progression-free survival (PFS) in relation to Fuhrman's grading (OS HR=2.25, PFS HR=2.93). RASSF1C levels were increased in ccRCC; no correlations with clinicopathological variables were found. We conclude that RASSF1C gene is not involved in ccRCC progression and we propose that the measurements of RASSF1A mRNA levels in paired tumor-normal kidney tissue could serve as a new prognostic factor in ccRCC.

Introduction: Urinary bladder urothelial cell carcinoma is one of the most commonly diagnosed cancers in Europe. After prostate, lung and colon cancers, bladder cancer rates as the fourth most common cancer in men in the world. Urinary bladder cancer detection, treatment, and staging have traditionally been based on an endoscopic examination - cystoscopy., Material and Methods: A Medline, and Web of Science database search was performed on September 2015 without setting time limits, using the terms 'bladder cancer' in conjunction with 'cystoscopy', 'diagnosis', 'detection', 'fluorescence', 'blue-light', 'PDD', 'narrow band imaging', 'molecular imaging', 'optical coherence tomography' or 'confocal laser endomicroscopy'., Results: The new imaging techniques can be classified according to their scope as macroscopic, microscopic, and molecular. Macroscopic techniques, such as narrow band imaging, are similar to white light cystoscopy; however, they help visualize even very minute lesions in the bladder mucosa by means of contrast enhancement. Microscopic imaging techniques, such as optical coherence tomography and confocal laser endomicroscopy, provide high-resolution cross-sectional views of vesicular tissues, which resemble images obtained by histopathological examination. Therefore, these are referred as 'optical biopsy'. Molecular imaging methods offer highly specific real-time visualization of cancer cells and their differentiation from healthy tissue, by combining optical imaging with fluorescent labeling of elements such as antibodies., Conclusions: In this article we present a review of studies and literature concerning modern optical diagnostic techniques for non-muscle-invasive bladder cancer. We present available technology with its advantages and disadvantages, and studies regarding its effectiveness.

Microcavity polaritons are two-dimensional bosonic fluids with strong nonlinearities, composed of coupled photonic and electronic excitations. In their condensed form, they display quantum hydrodynamic features similar to atomic Bose-Einstein condensates, such as long-range coherence, superfluidity and quantized vorticity. Here we report the unique phenomenology that is observed when a pulse of light impacts the polariton vacuum: the fluid which is suddenly created does not splash but instead coheres into a very bright spot. The real-space collapse into a sharp peak is at odd with the repulsive interactions of polaritons and their positive mass, suggesting that an unconventional mechanism is at play. Our modelling devises a possible explanation in the self-trapping due to a local heating of the crystal lattice, that can be described as a collective polaron formed by a polariton condensate. These observations hint at the polariton fluid dynamics in conditions of extreme intensities and ultrafast times.

Introduction: The aim of this study was to compare lymphatic drainage patterns detected with fluorescent dye indocyanine green (ICG) with the lymphatic drainage patterns detected with radiotracer (99m)Tc-nanocolloid in dynamic sentinel node biopsy (DSNB) procedures., Patients and Methods: Fourteen patients with penile cancer and no palpable lymph nodes were included prospectively for DSNB. First, on the day of surgery (99m)Tc-nanocolloid was injected at the lesion site. Then, single photon emission computed tomography (SPECT) lymphoscintigraphy was performed. ICG was injected in the same manner as the radiotracer just before the surgery. In all cases partial penectomy and DSNB were performed. Sentinel lymph nodes (SLNs) were localized intraoperatively using the gamma-ray detection probe for radiocolloid and near infrared fluorescence (NIRF) camera for ICG., Results: Transcutaneously, lymphatic nodes were identified in all 14 patients using the gamma probe and in 10 patients using the NIRF camera. After skin incision, fluorescent nodes were observed using the NIRF camera in the remaining 4 patients. The examination led to identification of 32 SLNs in total using technetium and ICG and additionally 3 more nodes visible only using ICG. All SLNs found using SPECT were also fluorescent. In 3 patients ICG enabled only approximate localization of the SLNs. Of 35 SLNs, 30 were negative and 4 were positive for metastasis., Conclusion: Our analysis of the effectiveness of ICG compared with radiocolloid in the DSNB for penile cancer indicates that they are comparable with some specific advantages and disadvantages. These findings must be studied further in a larger group of patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this study was to establish the prevalence of resistance to fluoroquinolones in Escherichia coli strains isolated from patients undergoing transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and to evaluate the incidence of possible infectious complications associated with this procedure. One hundred and four patients undergoing a TRUS-Bx in a single medical centre were prospectively enrolled in this study. In all patients, pre-biopsy rectal swabs were obtained. The analysis determined the antimicrobial susceptibility of E. coli strains to levofloxacin, ciprofloxacin and a panel of other antibiotics. Before biopsy, each of the men received a levofloxacin-based prophylaxis. Telephone follow-up was used to identify patients who had complications after TRUS-Bx. Fluoroquinolone-resistant strains were isolated from 9.62 % of the patients. In all cases, there were related to E. coli and all those strains were resistant to both levofloxacin and ciprofloxacin. Fluoroquinolones showed greater antimicrobial activity against E. coli (p < 0.05) than ampicillin, amoxicillin/clavulanate and cephalothin. Minor infectious complications occurred in three patients (2.91 %). The relation between the resistance of E. coli to fluoroquinolones and the risk of readmission, as well as infectious complications, was statistically significant (p < 0.05). Despite recent reports of increasing prevalence of fluoroquinolone-resistant E. coli and the associated increase of severe infectious complications, the presented results have not confirmed this phenomenon. Resistance to fluoroquinolones of E. coli strains isolated from rectal swab cultures prior to TRUS-Bx is the risk factor for readmission and infectious complications after this procedure.

The specifics of how galaxies form from, and are fuelled by, gas from the intergalactic medium remain uncertain. Hydrodynamic simulations suggest that 'cold accretion flows'--relatively cool (temperatures of the order of 10(4) kelvin), unshocked gas streaming along filaments of the cosmic web into dark-matter halos--are important. These flows are thought to deposit gas and angular momentum into the circumgalactic medium, creating disk- or ring-like structures that eventually coalesce into galaxies that form at filamentary intersections. Recently, a large and luminous filament, consistent with such a cold accretion flow, was discovered near the quasi-stellar object QSO UM287 at redshift 2.279 using narrow-band imaging. Unfortunately, imaging is not sufficient to constrain the physical characteristics of the filament, to determine its kinematics, to explain how it is linked to nearby sources, or to account for its unusual brightness, more than a factor of ten above what is expected for a filament. Here we report a two-dimensional spectroscopic investigation of the emitting structure. We find that the brightest emission region is an extended rotating hydrogen disk with a velocity profile that is characteristic of gas in a dark-matter halo with a mass of 10(13) solar masses. This giant protogalactic disk appears to be connected to a quiescent filament that may extend beyond the virial radius of the halo. The geometry is strongly suggestive of a cold accretion flow.

Introduction: Penile corporoplasty is a well-established treatment method of congenital penile deviation (CPD). Anatomical results are good with only slight differences between surgical procedures used. The disease however has huge influence on young male quality of life. This issue is not well analyzed in the literature., Aim: The aim of the study was to evaluate quality of life of the patients affected with CPD before and after the surgical treatment, Methods: Study population consisted of 107 patients with CPD referred for surgical management. Patients were evaluated with not only clinical assessment, but also by four questionnaires measuring various aspects of quality of life. They were: Short-Form Medical Outcomes, Sexual Quality of Life Questionnaire for Man, Beck Depression Inventory, and International Index of Erectile Function., Results: Quality of life measurements showed deep decrease in the general quality of life, sexual performance, depression scale, as well as in physical and mental health in men with CPD. All these parameters were restored to normal after the successful surgical treatment with any method., Conclusion: CPD deeply decreases the quality of life of the affected men in many aspects. Surgical treatment is able to repair the anatomical deformity and as well as significantly restore the patients' psychosocial well-being., (© 2015 International Society for Sexual Medicine.)

The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0-t , AUC0-∞ , and C max and lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 μg/mL (90 % CI 1.06, 1.25; p = 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p = 0.0375). The mean t max of paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean t max of sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p = 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

Prostate cancer (CaP) is a leading cause of cancer deaths in men worldwide. The alarming statistics, the currently applied biomarkers are still not enough specific and selective. In addition, pathogenesis of CaP development is not totally understood. Therefore, in the present work, metabolomics study related to urinary metabolic fingerprinting analyses has been performed in order to scrutinize potential biomarkers that could help in explaining the pathomechanism of the disease and be potentially useful in its diagnosis and prognosis. Urine samples from CaP patients and healthy volunteers were analyzed with the use of high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) in positive and negative polarity as well as gas chromatography hyphenated with triple quadruple mass spectrometry detection (GC-QqQ/MS) in a scan mode. The obtained data sets were statistically analyzed using univariate and multivariate statistical analyses. The Principal Component Analysis (PCA) was used to check systems' stability and possible outliers, whereas Partial Least Squares Discriminant Analysis (PLS-DA) was performed for evaluation of quality of the model as well as its predictive ability using statistically significant metabolites. The subsequent identification of selected metabolites using NIST library and commonly available databases allows for creation of a list of putative biomarkers and related biochemical pathways they are involved in. The selected pathways, like urea and tricarboxylic acid cycle, amino acid and purine metabolism, can play crucial role in pathogenesis of prostate cancer disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Clinical recurrence of prostate cancer manifested as a testicular mass is an extremely rare condition. We report a case of a 58-year-old patient with a testicular tumor who underwent orchiectomy 7 years after radical prostatectomy. The pathology analysis confirmed metastasis from prostate carcinoma. After one year, the patient had no signs of biochemical and clinical recurrence. This argues for considering metastasectomy in such patients., (© 2015 S. Karger AG, Basel.)

There is no data on reference gene (RG) selection in metastatic clear-cell renal cell carcinoma (mccRCC) for quantitative PCR (qPCR) data normalization. We aimed at selecting the most stable RG for further determination of new prognostic markers. Thirty-five nonmetastatic and 35 mccRCC patients undergoing radical nephrectomy were included. Paired primary tumor (T, n = 70) and normal (C, n = 70) kidney fragments were collected; from 12 out of 35 mccRCC cases, we also collected metastasized regional lymph nodes and adrenal gland tissues (M, n = 12). After RNA extraction, reverse transcription and qPCR were performed. Samples were divided into four analyzed groups. Fifteen candidate RGs were tested by RefFinder tool and manual statistics. To present the importance of RG selection, TP53 gene expression levels in samples were normalized with the use of RG data. RPL13 gene was the most stable RG in analysis of 35 primary tumor nonmetastatic versus 35 mccRCC samples and matched metastasized T/C/M samples (n = 12, each group). GUSB was the most suitable RG in total 152 samples and in paired T and C (n = 140) kidney samples. Expression of GUSB, RPL13, and the RPL13 + RPLP0 pair were independent of clinical/sample variables. Normalization of TP53 expression levels showed variability of GAPDH and ACTB assays. GUSB or RPL13 assays should be used in mccRCC for qPCR data normalization whereas GAPDH and ACTB assays should be avoided. Prior RG studies should precede each qPCR gene expression study since RG selection is associated with the origin and proportion of specimens.

Background: Diabetes is one of the most common metabolic diseases in the world, which may influence changes in the pharmacokinetics and pharmacodynamics of drugs. Sunitinib is a tyrosine kinase inhibitor (TKI) broadly used for treatment of numerous cancers, which exhibits the side hypoglycaemic effect. The aim of the study was a comparison of concentrations and pharmacokinetics of sunitinib after a single administration in rabbits with hyperglycaemia and normoglycaemia (control group). Additionally, the effect of sunitinib on glucose levels was investigated., Methods: The research was carried out on a control group (n=6) and a group of rabbits with diabetes (n=6). The rabbits were treated with sunitinib in the oral dose of 25mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with validated HPLC method with UV detection., Results: The comparison of the sunitinib Cmax and AUC0-∞ in the diabetic group with the control group gave the ratios of 1.63 [90% confidence interval (CI) [1.59; 1.66] and 2.03 [1.97; 2.09], respectively. Statistically significant differences between the analyzed groups were revealed for Cmax (p=0.006), AUC0-∞ (p=0.0088), and AUCkel (p=0.009). The maximum glycaemia drop of 14.4-69.6% and 15.4-33.5% was observed in the diabetic animals and in the control group, respectively. The glycaemia values returned to the initial values in 24h after the administration of the drug., Conclusions: The research proved the significant influence of diabetes on the pharmacokinetics of sunitinib and it confirmed the hypoglycaemic effect of the TKI in diabetic rabbits and in normoglycaemia., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Objectives: At present it is known that the adjustment of the anticancer therapy to the circadian rhythms in tissues reduces the toxicity of the treatment. Chronotherapy also increases the efficacy of the anticancer treatment, which has been proved for many drugs. Sunitinib is a tyrosine kinase inhibitor, which is broadly used for the treatment of numerous cancers. The aim of the study was a comparison of the concentrations and pharmacokinetics of sunitinib after a single administration to rabbits at 08:00 (control group) and 20:00. Additionally, the effect of sunitinib on glucose levels was investigated., Materials and Methods: The research was carried out on two groups of rabbits: I08:00, a group with the drug administered at 08:00 (n=8) and II20:00, a group with the drug administered at 20:00 (n=8). The rabbits were treated with sunitinib at an oral dose of 25 mg. Plasma concentrations of sunitinib and its metabolite (SU12662) were measured with a validated HPLC method with UV detection., Results: The comparison of the sunitinib Cmax and AUC0-t in the group with sunitinib administered at 20:00 with the control group gave the ratios of 2.20 (90% confidence interval (CI) (2.17; 2.22) and 1.64 (1.61; 1.68), respectively. Statistically significant differences between the groups under analysis were revealed for Cmax (p < 0.0001), AUC0-t (p = 0.0079), AUC0-∞ (p = 0.0149), and tmax (p = 0.0085). The mean glycemia drop was higher in group I08:00. than in group II20:00 (22.7% vs. 14.3%; p = 0.0622). The glycemia values returned to the initial values in 24 h after the administration of the drug in both groups., Conclusions: The research proved a significant influence of the time-of-day administration on the pharmacokinetics of sunitinib.

A cyclic form of N(6)-threonylcarbamoyladenosine bearing an oxazolone moiety (ct(6)A) was discovered very recently at the position 37 in several tRNA sequences. Our study on the synthesized 5',3',2'-O-acetylated derivative of ct(6)A confirmed high stability of the modified nucleoside under physiological conditions (PBS buffer, pH 7.4) and revealed remarkable stability of the oxazolone ring in acidic (100mM HCl, pH 1) and basic (0.1mM NaOH, pH 10) conditions. This feature may allow for the post-synthetic conversion of t(6)A into ct(6)A in assembled oligoribonucleotides., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although a variety of techniques have been used to manage the distal ureter during laparoscopic radical nephroureterectomy (LNU), a consensus has not yet been established. Recently, some authors have used a single-port transvesical approach to excise the distal ureter and bladder cuff following LNU. The aim of the study was to present our initial experience in "en bloc" dissection of the distal ureter and bladder cuff during LNU, using a transvesical single-port approach (T-LESS) and standard laparoscopic instruments. From April to October 2012, 5 patients aged 45 to 73 years with upper urinary tract urothelial tumors were subjected to LNU/T-LESS. After a standard LNU was performed, a TriPort+(®) device was introduced into the bladder and the pneumovesicum was established. A bladder cuff with a distal ureter was dissected and put in the paravesical tissue. The bladder wall defect was closed with the V-loc(®) 3/0 suture. The LNU was then completed in the flank position. All procedures were completed successfully. No significant blood loss or complications were observed. The mean operative time was 250 min (range: 200-370) for a total procedure and 59 min (range: 42-80) for the T-LESS stage. The postoperative hospital stay was 5.2 days (range: 4-9). Pathologic examination revealed no positive margin in any of the cases. The LNU/T-LESS approach is an efficient and safe procedure. A well-visualized dissection of the distal ureter, closing the defect of the bladder, the use of standard laparoscopic instruments and a good cosmesis are advantages of the method.

Introduction: Near infrared (NIR) technology has recently garnered much interest as a tool for intraoperative image-guided surgery in various surgical sub-disciplines. In urology, although nascent, NIR technology is also fostering much enthusiasm. This review discusses the two major fluorophores, indocyanine green (ICG) and methlyene blue (MB), with NIR guidance in experimental and clinical urology. The authors aim to illustrate and analyze the currently available initial studies to better understand the potential and practicability of NIR-guided imaging in the diagnosis and surgical outcome improvement. In the first part of the study we analyzed problems associated with sentinel lymph node biopsy, NIR-guided detection and imaging of tumors., Material and Methods: PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences., Results: Although NIR-guided ICG and MB are still in their initial phases, there have been significant developments in major domains of urology, including uro-oncological surgery: 1) sentinel lymph node biopsy, 2) detection and imaging of tumors., Conclusions: Much like in other fields of surgical medicine, the application of NIR technology in urology is at its early stages. Therefore, more studies are needed to assess the true potential and limitations of the technology. However, initial developments hint towards a pioneering tool that may influence various aspects of urology.

Introduction: The repair of complex urethrorectal fistulas, which can be the result of treating prostate cancer with radical prostatectomy, is a big problem in urology and its final result is not always satisfactory. There are no universally accepted methods for repairing such fistulas. In our work we present a retrospective analysis of patients treated for urethrorectal fistulas after previous radical prostatectomy. The methods used were the initial excision and suture of the fistula, or a gracilis muscle flap interposition., Material and Methods: In the years 2000-2012, four patients were treated because of urethrorectal fistulas after radical prostatectomy. In two patients, open radical prostatectomy had been performed. Two other patients had been operated laparoscopically. Two patients had a primary fistula repair. They were operated using anterior perineal access. Two others were treated with the use of a gracilis muscle flap., Results: During the follow up, there was no recurrence of fistulas. Medium follow up for the first two patients was 120 and 156 months, and follow up of two other patients was 16 and 23 months. Until now, there were no final postoperative complications., Conclusions: Repair of the fistulas requires an individual approach to each case. Excision and suturing of the fistula gives a very good final result, especially when the primary reconstruction is performed. Repair of urethrorectal fistula using a gracilis muscle flap appears to be an excellent option in cases of complex recurrent fistulas. It is also associated with low morbidity in patients and a high success rate.

Introduction: In the second part of this paper, concerning the use of invisible near infrared light (NIR) fluorescence with indocyanine green (ICG) and methylene blue (MB) in urology, other possible uses of this new technique will be presented. In kidney transplantation, this concerns allograft perfusion and real time NIR-guided angiography; moreover, perfusion angiography of tissue flaps, NIRF visualization of ureters, NIR-guided visualization of urinary calcifications, NIRF in male infertility and semen quality assessment. In this part, we have also analysed cancer targeting and imaging fluorophores as well as cost benefits associated with the use of these new techniques., Material and Methods: PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences., Results: Although NIR-guided ICG and MB are still in their initial phases, there have been significant developments in a few more major domains of urology, including 1) kidney transplantation: kidney allograft perfusion and vessel reconstruction; 2) angiography perfusion of tissue flaps; 3) visualization of ureters; 4) visualization of urinary calcifications; and 5) NIRF in male infertility and semen quality assessment., Conclusions: Near infrared technology in urology is at its early stages. More studies are needed to assess the true potential and limitations of the technology. Initial studies show that this pioneering tool may influence various aspects of urology.

We consider a phase transition from an antiferromagnetic to a phase separated ground state in a spin-1 Bose-Einstein condensate of ultracold atoms. We demonstrate the occurrence of two scaling laws, for the number of spin domain seeds just after the phase transition, and for the number of spin domains in the final, stable configuration. Only the first scaling can be explained by the standard Kibble-Żurek mechanism. We explain the occurrence of two scaling laws by a model including postselection of spin domains due to the conservation of condensate magnetization.

Introduction: Despite the introduction of better diagnostic tools, very large kidney tumors are still not so rare in our country. The paper presents our experience in the treatment of 12 patients with kidney tumors larger than 14 cm in size., Material and Methods: Between spring 2009 and autumn 2011, radical nephrectomies were performed in 12 patients due to a large kidney tumor (larger than 14 cm in size). Symptoms (hematuria, weight loss, anemia, etc.) were not present in all the patients, but the kidney tumor was confirmed by imaging studies (ultrasound, CT, MRI) in all of them., Results: Full recovery was observed with no severe complications in all of the patients treated with radical nephrectomy. Pathological staging was correctly established by imaging studies in all of them. After a few months, five of patients (41.6%) required systemic therapy due to lymph node involvement., Conclusions: Patients with large kidney tumors should be treated in selected medical centers that have experience in the treatment of such cases. Radical nephrectomy has to be the method of choice in the treatment of patients with this kind of tumor and its diameter should not disqualify from surgical treatment, which is still the only chance for the patients to be cured, as no adjuvant chemotherapy treatment has proved to be significantly effective.

Large cell calcifying sertoli cell tumor (LCCSCT) is an exceptionally rare neoplasm originating from sperm cord cells. The tumors have relatively low malignant potential and unlikely proceed to metastasis formation. The lesions may occur in an isolated form or in ca. 40% of cases may be associated with genetic abnormalities, by and large Peutz-Jeghers syndrome and Carney complex. At presentation, 20% of LCCSCT cases are bilateral and/or multifocal. Owning to characteristic skin lesions and particular hyperechoic ultrasound image of the tumor, preliminary diagnosis of the syndromic LCCSCT is possible in the preoperative period. Consequently, testicle organ-sparing procedure can be attempted, which is especially justified in bilateral lesions. Here, we report a case of a bilateral LCCSCT in a 20-year-old man with atypical Peutz-Jeghers syndrome due to amplification of the exon 1 of STK11 gene who was successfully treated with bilateral testicle-sparing tumorectomies.