Репозиторий Университета

© 2020 The Authors Background: Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent. Objective: The aim of this study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020. Methods: We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design. Results: Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers. Conclusions: A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.

© 2020 The Authors Background: Since the first report by Perry et al. (1955), most studies affirmed the hypertensive effects of cadmium (Cd) in humans. Nonetheless, conclusions between studies remain inconsistent. Objective: The aim of this study was to reevaluate the evidence for a potential relationship between Cd exposure and altered blood pressure and/or hypertension, focusing on studies published between January 2010 and March 2020. Methods: We reviewed all observational studies from database searches (PubMed and SCOPUS) on Cd exposure and blood pressure or hypertension. We extracted information from studies that provided sufficient data on population characteristics, smoking status, exposure, outcomes, and design. Results: Thirty-eight studies met our inclusion criteria; of those, twenty-nine were cross sectional, three case control, five cohort and one interventional study. Blood or urinary Cd levels were the most commonly used biomarkers. Conclusions: A positive association between blood Cd levels and blood pressure and/or hypertension was identified in numerous studies at different settings. Limited number of representative population-based studies of never-smokers was observed, which may have confounded our conclusions. The association between urinary Cd and blood pressure and/or hypertension remains uncertain due to conflicting results, including inverse relationships with lack of strong mechanistic support. We point to the urgent need for additional longitudinal studies to confirm our findings.

Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.

© 2019, Pediatria Ltd. All rights reserved. Pyelonephritis treatment in children with neurogenic bladder (NB) has a number of peculiarities, which include incomplete bladder emptying after self-urination and causing difficulties in determining treatment tactics for primary care pediatricians. Residual urine is a risk factor for development and relapse of chronic pyelonephritis, and urinary incontinence is also a medical and social problem. The article presents an example of observing an 8-year-old girl after 2 years of ineffective treatment for chronic pyelonephritis with mistakes in primary diagnosis. It provides the analysis of 3 months treatment and examination of the child with NB, including monitoring of urination functional productivity. The scheme of combined correction of inflammatory process and urinary tract dysfunction is presented. A systematic step-by-step approach to diagnosis and treatment of recurrent pyelonephritis in children with NB allows to increase therapy efficacy and improve patient's quality of life. The presented clinical case differs because bladder dysfunction manifested itself at the age of 8 years with an increase of bladder residual volume. Peculiarity of pathogenetic mechanisms of this pathology development in the described observation is a combination of delayed mature urination formation and manifestation of acute pyelonephritis, which required a non-standard approach to diagnosis and treatment.

© 2018, Pleiades Publishing, Ltd. The gene for Kunitz peptidase inhibitor-like protein (KPILP) contains nested alternative open reading frame (aORF) that controls expression of the maternal mRNA. The content of NbKPILP mRNA in intact leaves of Nicotiana benthamiana plant is low but increases significantly upon extended dark exposure or when foreign nucleic acid is overexpressed in the cells. The NbKPILP gene promoter along with the expressed nested aORF are likely to play an important role in maintaining the levels of NbKPILP mRNA. To elucidate the role of NbKPILP promoter, we isolated a fragment of N. benthamiana chromosomal DNA upstream of the NbKPILP transcription start, sequenced it, and created constructs in which reporter E. coli uidA gene coding for β-D-glucuronidase (GUS) was placed under control of the NbKPILP promoter. By assessing the efficacy of uidA mRNA synthesis directed by the NbKPILP promoter and 35S promoter of the cauliflower mosaic virus in a transient expression system, we showed that the levels of GUS accumulation were comparable for both promoters. Prolonged incubation of the agroinjected plants in the darkness stimulated accumulation of the uidA mRNA directed by the NbKPILP promoter. Our experiments indicate that along with regulation at the transcriptional level, expression of NbKPILP mRNA can be affected by expression of the nested aORF controlled by the polypurine block (PPB) located upstream of its start codon, since introduction of mutations in the PPB resulted in significant accumulation of the NbKPILP mRNA. Nucleotide replacement in the aORF start codon led to the drastic increase in the amounts of NbKPILP mRNA and its protein product.

AIM: To evaluate early prostate cancer cryoablation functional and oncological results in comparison with results of extraperitoneoscopic radical prostatectomy. MATERIALS AND METHODS: We analyzed early results of surgical treatment of 285 patients with prostate cancer: 42 of them had undergone total cryoablation (Group 1) while the rest of them had been treated by radical laparo- and extraperitoneoscopic prostatectomy. For comparative assessment of prostate cryoablation results, 42 patients from Group 2 randomized in accordance with their age, stage of disease, Gleason, prostate-specific antigen, and prostate volume were selected. In compliance with the results of pre-surgical examination, all the patients had low oncological risk and were not concerned in sexual function. Volume of prostate was from 22 to 65 cm3, prostate-specific antigen level was from 4.1 to 10 ng/mL, and level of neoplastic process differentiation using Gleason grading system was from 6 to 7a (3 + 4) scores. RESULTS: Patients after prostate cryoablation in early post-surgical period felt lower intensity of postoperative pain compared with those who had undergone prostatectomy. Follow-up period up to 12 months manifested significant true reduction of prostate-specific antigen level in both groups of patients. Frequency of stress-induced enuresis in Group 1 was not observed. CONCLUSION: Radical prostatectomy is still the traditional treatment of choice in the case of localized prostate cancer. But we can draw the conclusion that cryoablation is an effective low-invasive method for treatment of low oncological risk patients, which gives the opportunity both to achieve good oncological results and to preserve high life quality.

© 2018 Elsevier B.V. Although recent Cannabis use is widely reported to be associated with drug-related traffic accidents, the evidence that Cannabis users show an increased risk of being involved in road crashes is still not unequivocally proved. The purpose of the present work is to provide an objective assessment of this hypothesis, by comparing the frequency of occurrence of positive urine analyses in drivers involved in traffic accidents (n = 1406) with that observed in a control population undergoing mandatory urine drug testing (n = 1953). Urine analyses for drugs of abuse were performed by screening immunometric techniques followed by confirmation with UHPLC-QQQ MS, adopting a cut-off concentration for THC-COOH of 15 ng/mL. A case was classified as “positive” when a driver admitted to hospital for road traffic injuries showed urine concentrations of THC-COOH higher than the cut-off. All samples showing positive results for any other controlled drug in urine or blood alcohol concentrations >0.5 mg/mL were excluded from the study. Subjects positive to THC-COOH, and negative to all the other tested substances were 116 in Group 1 (8.2%) and 16 in Group 2 (0.8%). Subjects resulting negative to any tested substances were 1290 in Group 1 and 1937 in Group 2. The frequency of THC-COOH detection in the two groups was compared by using the “chi square” test, which resulted = 119.57, i.e. highly significant (P <<< 0.01). The Odds Ratio of the two groups was =10.88, showing a high degree of association between the presence of THC-COOH in urine and the occurrence of traffic accidents (P < 0.0001). The presented data, proving a high degree of association between Cannabis use and the occurrence of traffic accidents with injuries of the driver, support the use of urine testing for Cannabis in the procedures for the issuing of the driving licence, particularly in the case of subjects formerly or presently using Cannabis. This finding looks even more relevant in the present times, because of the increasing success of the policies of legalization of Cannabis for medical and non-medical purposes.

© Allerton Press, Inc., 2018. A technique of extracting cotinine in urine and wastewaters, followed by its quantitative determination, using high performance liquid chromatography combined with tandem mass-spectrometric detection is presented. The method is characterized by low detection limits and high levels of efficiency and sensitivity. The optimal conditions for the solid-phase extraction of cotinine from urine and wastewaters are found. This technique makes it possible to reliably estimate the content of cotinine in the urine of active and passive smokers and in wastewaters.

© 2017 Elsevier B.V. The use of polymeric carriers to deliver hydrophobic photosensitizers has been widely discussed as a way to improve both fluorescence diagnostic and photodynamic therapy (PDT) of cancers; however, the photophysical and pharmacokinetic parameters, as well as the PDT activity, of such modifications have, until now, only been poorly investigated. The purpose of the present study was to explore the efficacy of PDT with the formulation of the photosensitizer chlorin e6 (Ce6) in combination with polyvinyl alcohol (PVA) in comparison with Ce6 alone and with the clinical drug, Photodithazine in a mouse tumor model. We also investigated the photoactivity of the Ce6-PVA in a model reaction of tryptophan oxidation, analyzed the polymer–Ce6 interaction using fluorescence spectroscopy and atomic-force microscopy, and tested the phototoxicity in vitro. Using fluorescence imaging in vivo we found that injection to mice of Ce6 in a formulation with PVA resulted in a higher tumor-to-normal ratio and greater photobleaching when compared with either the use of Ce6 alone, or with the effects of Photodithazine. Tumor growth study and histological examination of CT26 tumors revealed fast, reproducible tumor regression and more advanced necrosis after PDT with Ce6-PVA. The higher photoactivity of the Ce6-PVA complex was confirmed in a model reaction of tryptophan oxidation and in cultured cells. Therefore, encapsulation of Ce6 in PVA represents a promising strategy for further increasing the selectivity and efficacy of PDT.

Background Urethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model. Methods Autologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction. ResultsAutologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo. Conclusions Autologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.

Background Urethral reconstruction is one of the great surgical challenges for urologists. A cell-based tissue-engineered urethra may be an alternative for patients who have complicated long strictures and need urethral reconstruction. Here, we demonstrated the feasibility of using autologous urine-derived stem cells (USCs) seeded on small intestinal submucosa (SIS) to repair a urethral defect in a rabbit model. Methods Autologous USCs were obtained and characterized, and their capacity to differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs) was tested. Then, USCs were labeled with PKH67, seeded on SIS, and transplanted to repair a urethral defect. The urethral defect model was surgically established in New Zealand white male rabbits. A ventral urethral gap was created, and the urethral mucosa was completely removed, with a mean rabbit penile urethra length of 2 cm. The urethral mucosal defect was repaired with a SIS scaffold (control group: SIS with no USCs; experimental group: autologous USC-seeded SIS; n = 12 for each group). A series of tests, including a retrograde urethrogram, histological analysis, and immunofluorescence, was undertaken 2, 3, 4, and 12 weeks after the operation to evaluate the effect of the autologous USCs on urethral reconstruction. ResultsAutologous USCs could be easily collected and induced to differentiate into UCs and SMCs. In addition, the urethral caliber, speed of urothelial regeneration, content of smooth muscle, and vessel density were significantly improved in the group with autologous USC-seeded SIS. Moreover, inflammatory cell infiltration and fibrosis were found in the control group with only SIS, but not in the experimental autologous USC-seeded SIS group. Furthermore, immunofluorescence staining demonstrated that the transplanted USCs differentiated into UCs and SMCs in vivo. Conclusions Autologous USCs can be used as an alternative cell source for cell-based tissue engineering for urethral reconstruction.