Репозиторий Университета

© 2018 Russian Transplant Society. All Rights Reserved. Aim. To study the efficacy and safety of the use of paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin in liver recipients with recurrence of HCV 1 genotype after transplantation. Materials and methods. The study included 46 patients after orthotopic liver transplantation with recurrence of HCV 1 genotype. 37 patients completed a 24-week course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin. The effectiveness of the therapy was calculated as the proportion of patients who achieved aviremia 12 weeks after the end of the course of treatment. The safety of therapy was assessed by the number of adverse events that occurred during the course of antiviral therapy. Results. A sustained virologic response at 12 weeks after the end of the course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir, reached 100% of the recipients of the liver. Reduction in the intensity of cytolytic and cholestatic syndromes was noted at week 4 of therapy. Adverse events were recorded in 56.7% of the subjects, mostly they were not severe and were stopped on their own. Acute cellular rejection of the transplant developed in 1 patient (2.7%). There have been no cases of irreversible liver transplant dysfunction or death of the recipient. The conclusion. The use of paritaprevir, ritonavir, ombitasvir and dasabuvir is safe and effective in the treatment of relapse of HCV infection of 1 genotype after liver transplantation.

© 2018 Silina et al. Aim: The purpose of this study was to examine the role of free radical oxygen and peroxide-lipid processes along with conducting the study of blood flow level and oxygen saturation of facial tissues in patients of different ages with varying degrees of involutional changes in the skin of the face and neck. Materials and methods: One hundred and fifty-three people (84.3% women and 15.7% men) aged from 26 to 78 years with varying degrees of involutional changes in facial skin were examined. The clinical and laboratory evaluation was carried out dynamically and included various indicators of free radical processes, objective and subjective clinical visualization, and laser Doppler flowmetry (LDF) of the facial skin and transcutaneous oximetry (TcpO2) performed at 10 points on the face. To assess the state of free radical processes, the authors investigated the basal indicator of chemiluminescence intensity (ICb), the intensity of chemiluminescence stimulated (ICs) by zymosan, the activity coefficient (AC) of chemiluminescence, antiperoxide activity of plasma, and malondialdehyde (MDA). Results: With aging, the imbalance of the oxygen constituents of free radical processes grows with the increase in ROS. Proportional to age, the ICs increased 2.1 times on average in people older than 55 years compared to that in people younger than 30 years and ICb decreased by 1.8 times. As a result, the AC increased by 5.6 times. This correlates with involuntary skin changes and with regression of microcirculation and TcpO2. According to LDF, it was established that average total blood flow in people younger than 30 years and people older than 55 years was 8.1 and 6.4 mL/min, respectively The difference between the indicators of TcpO2 in people younger than 30 years and people older than 55 years was 1.6 times (average 56 vs 35 mm Hg). The stability of the indicators of the peroxide-lipid link of oxidative stress in different age groups demonstrated that the activation of ROS formation in mitochondria is not a cause but a consequence of microcirculation and metabolic processes in the face and neck and aging in general. Conclusion: The tissue metabolism and microcirculation parameters naturally regress with aging, which is associated with the increase of ROS. The excess of species leads to the intensification of peroxide processes. This, in turn, is reflected in the aesthetic appearance manifested by aging.

© 2018 Sychev et al. Purpose: The aim of this study was to determine the impact of ABCB1 (MDR1) rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian patients. Patients and methods: The 12-week study included 100 patients. Patients with the newly diagnosed stage I–II hypertension (HT) were recruited to complete genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy. The initial dose was 5 mg/day. Four office blood pressure measurements, two 24-hour noninvasive ambulatory blood pressure measurements, and questionnaires of Tsvetov were used to evaluate the efficacy and safety of amlodipine. Results and conclusion: The highest antihypertensive effect in combination with the lowest incidence of adverse reactions was observed in the TT group, while patients with the CC genotype showed a low antihypertensive effect and the highest incidence of adverse effects. Patients with the CC genotype presented with adverse effects predominantly in the form of edema. A total of 33 patients reached the target blood pressure (SBP <140 mmHg; DBP <90 mmHg): two patients with the CC genotype (12%); 18 patients with the CT genotype (34%); and 13 patients with the TT genotype (43%). The intergroup differences were: CC vs CT, P=0.02; CC vs TT, P=0.02; and CT vs TT, P=0.05. The results of this study indicate the potential of pharmacogenetic testing for rs1045642 SNP when prescribing amlodipine for the first time in Caucasian patients with stage I–II arterial HT.

© 2018 Stavropol State Medical University. All Rights Reserved. The cytological picture of oral tissues in experimental animals was studied when creating a cariogenic model with a formed artificial defect of hard tissues (Black class V), filled with a restorer filling material Restavrin coated with Easy Glaze sealant and without it. The intensification of the formation of plaque and the manifestation of the inflammatory process in a group of animals with defects, but without coating with sealant was revealed by the 30th day of observation. By this time of the experiment, the number of segmented neutrophils and desquamated epithelium cells sharply increased while the ratio of dead to live cells increased, which increases the degree of cariogenic danger and intensity of inflammation in the area of buccal epithelium, gums and periodontium. A mandatory coating of a photo-composite restoration with a sealant is recommended, which serves as a barrier that protects the filling material from the influence of exogenous factors, preserves the aesthetic and mechanical qualities of composite restorations.

©2018 International Medical Press. Despite very high efficacies of direct-acting antivirals (DAAs) reported in clinical trials, treatment failure in real-life practice can occur in 5–10% of cases and is mostly associated with emergence of resistance-associated substitutions (RASs). Little is known about the efficacy of retreatment in these patients, especially in those with decompensated cirrhosis, and only a few retreatment studies have been performed so far. Here we present case reports of successful sofosbuvir-based treatment in patients with advanced class B cirrhosis with prior pegylated interferon/ribavirin and all-oral DAA failure with multiclass drug resistance. HCV resistance testing at failure was performed to guide the choice of salvage therapy.

©2018 International Medical Press. The publisher would like to report an error that appeared in a recently published article [1]. The word ‘dasabuvir’ should have read ‘daclatasvir’ in the paragraph regarding Patient 3. The correct sentence is as follows: ‘The patient was treated twice with sofosbuvir and daclatasvir for 12 weeks and then with RBV for 24 weeks’. This has been corrected as of 10 October 2018. The authors apologize for this error.

© 2018 Medical Education. All Rights Reserved. Chronic rhinosinusitis with nasal polyps (CRS NP) is the most prevalent ear, nose, and throat (ENT) disorder in cystic fibrosis (CF) patients. CRS NP can occur in CF children at the age of ≥ 8 months and becomes the chronic disease. Tenacious secret and bacterial infection cause obstruction, edema and hypoxia of paranasal sinuses and contribute to significant morbidity in CF patients. The active monitoring and treatment of CRS NP aimed at improvement of the aeration of paranasal sinuses, mucociliary clearance, and the control of chronic upper airway infection are necessary. Functional Endoscopic Sinus Surgery (FESS) may be the method of choice if surgical treatment is considered. FESS facilitates paranasal sinuses drainage. Due to recurrent course of CRS NP in most CF patients, lifelong follow-up by an ENT specialist and postoperative management using topical steroids and/or antibiotics are required.

© 2018 Ima-Press Publishing House. All Rights Reserved. Up to 15% of patients with secondary brain tumors of unknown primary are admitted to a neurosurgery department. Identification of a primary tumor site on the basis of surgical material immunophenotyping in routine clinical practice has a significant potential; however, this requires systematization. Objective: to detect the primary focus of brain carcinoma. Patients and methods: Surgical specimens from 7 patients with brain tumor of unknown primary were investigated using light optical microscopy and an immunohistochemical (IHC) panel including EMA, CK AE1/3, CK7, CK5/6, GFAP, S-100, Vimentin, p63, TTF-1, Uroplakin III (UPIII), CDX2, and Her2/neu. Results and discussion: A study using the IHC panel made it possible to obtain the following tumor phenotypes in the patients: CK5/6+, p63+, CK7+, UPIII+ (urothelial cancer) (n=3); CK5/6-, CK7+, TTF-1+, CDX2- (lung adenocarcinoma) (n=2); CK5/6+, p63+, CK7-, UPIII, TTF-1- (squamous cell carcinoma) (n=1), and CK5/6-, CK7+, TTF-1-, CDX2-, Her2/neu+ (breast cancer) (n=1). Evidence of the primary focus of the tumors was subsequently confirmed by instrumental techniques in all cases when cancer of the breast, lung and urinary system was directly sought. The findings were used to elaborate an algorithm for the differential diagnostic immunophenotyping of brain metastases. Conclusion: The primary focus of brain carcinoma was detected in all cases on the proposed IHC panel. The systematized algorithm for differential diagnostic immunophenotyping can be used in clinical practice.

©2018 International Medical Press. Despite very high efficacies of direct-acting antivirals (DAAs) reported in clinical trials, treatment failure in real-life practice can occur in 5–10% of cases and is mostly associated with emergence of resistance-associated substitutions (RASs). Little is known about the efficacy of retreatment in these patients, especially in those with decompensated cirrhosis, and only a few retreatment studies have been performed so far. Here we present case reports of successful sofosbuvir-based treatment in patients with advanced class B cirrhosis with prior pegylated interferon/ribavirin and all-oral DAA failure with multiclass drug resistance. HCV resistance testing at failure was performed to guide the choice of salvage therapy.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Purpose. To determine the role of MSCT in the development of pneumoconiosis. Materials and methods. A total of 109 patients with the pneumoconiosis: silicosis and pneumoconiosis from mixed dust were examined at the Clinical IRIOH (Moscow) and the Orenburg Regional Clinical Hospital №2 (Orenburg). Patients underwent complex clinical and laboratory research, external respiration function examination, bronchos-copy and radiation examination. Results. Concomitant pulmonary tuberculosis was detected in 11%. Dissemination and interstitial changes were determined. Foci were located chaotically, perilymphatically. At the time of the initial study, the fusion of foci was 67.5%, with a dynamic study - in 100%. Interstitial changes were characterized by thickening of intra-lobular and interlobular interstitium. 19 patients had fibrous conglomerates, which were heterogeneous due to the presence of calcifications, necrosis and sometimes destruction cavities, which were later replaced by fibrotic changes. 57 patients were observed in dynamics during 3-19 years. 44 patients had a negative dynamics. There was no connection with the experience in the conditions of the impact of aerosol and profession. A great influence was exerted by the dispersion of dust and the concentration of silicon dioxide in it. Progression was characterized by an increase in the number of foci, their size, fusion and formation of fibrosis areas, an increase in the thickness of interstitium. Conclusions. Pneumoconiosis has progression even in the post-contact period. The growth of fibrotic changes led to emphysema of the lungs and respiratory failure. The dust dispersion affects the character of the progression.

© 2018 Ima-Press Publishing House. All Rights Reserved. This review provides information on prospects for using the antidepressant agomelatine in neurological practice. The drug has a unique receptor profile, being a melatonin receptor type 1 and 2 agonist and a serotonin receptor subtype 2C antagonist. Due to this and in addition to antidepressant action, the drug has a number of other effects, such as analgesic, anti-apathetic, anti-asthenic, procognitive, anxiolytic, and sleep-normalizing ones, which are of great importance in the treatment of neurological diseases. There are clinical and experimental data that prove the high efficiency and safety of agomelatin in the follow-up of patients with post-stroke depression, Parkinson's disease, Alzheimer's disease, Pick's disease, Huntington's disease, chronic fatigue syndrome, and pain syndromes.

© 2018 Russian Electronic Journal of Radiology. All Rights Reserved. Purpose. This case describes the role of radiology diagnostic methods in patients with congenital right transposition of the aortic arch. Due to the underestimation of radiology data, congenital right transposition of the aortic arch was not detected before surgery, which led to the selection of inadequate surgical access and technical difficulties that were successfully overcome.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Purpose. To show the difficulty of diagnosis and treatment of atypical course of tuberculous empyema, when the process was complicated by tuberculosis of the chest, destruction of the diaphragm and penetration into the liver. Results. After chest MSCT scan, tuberculosis was suspected. The patient successfully underwent surgery: Pleurectomy with chest wandering abscess excision, resection of the VII rib and abdominal wandering abscess excision combined with the diaphragm and liver resection. The postoperative period was uncomplicated. During examination 4 years after surgery the patient was in a satisfactory condition, has ability to work, was transferred to group III dispensary tuberculosis registration. Discussion. Diagnosis and treatment of pleural empyema in some cases is difficult and, sometimes, requires differentiation from the oncological process. We have not found cases of tuberculous empyema spread of in the abdominal cavity with penetration into the liver in the literature. Conclusion. MSCT scan allowed to timely diagnose the atypical course of tuberculous empyema.

© 2018 Vladimir A. Chistyakov, Alexander V. Usatov, Aleksander I. Klimenko, Maria A. Kolosova, Eugenia V. The abundance of potential genotoxins makes it necessary to improve microbial test systems that allow to identify these substances quickly. At the same time, the methodology of metabolic activation of promutagens in vitro is very important. Microsomal preparations of rodents, which are generally used for that, have significant disadvantages associated with the potential health risks of the inducers of the metabolism of microsomal cytochromes. For the metabolic activation of promutagens, we have developed a protocol of microsomal homogenate fraction (S-9) preparation. We propose to complement the set of methods for quality control of feeds for valuable and rare chicken breeds with the Ames test (Salmonella/microsome) using the activated chicken hepatic S-9 homogenate fraction.

© 2018 Izdatel'stvo Meditsina. All rights reserved. The main objective of laboratory diagnosis of a diphtheria is identification of the causative agent by means of the minimum quantity of diagnostic tests for obtaining the authentic answer in the most short time. One of the major stages is capture and delivery of pathological material on which the efficiency of carrying out and timeliness of issue of the final answer depends. Considering emergence in the market of commercial liquid transport mediums, assessment of their efficiency for diagnosis of diphtheria is advisable. In the real work the pilot studies allowing to predict efficiency of use of the commercial transport liquid medium £-Transwab® with the liquid medium of Ames in two systems - with the standard applicator (system 1) and with the thin extended tampon for sampling from narrow cavities - urethral and nazofarengialny are conducted (system 2). In a research used a control toxigenic strain of Corynebacterium diphtheriae of a biovar of gravis No. 665. In an experiment "imitated" operating conditions of the medical organizations for storage of tampons with pathological material on diphtheria before their transportation in laboratory - on a table at the room temperature (6 and 20 hours), in the refrigerator (6 and 20 hours), in the thermostat (6 and 20 hours). After an incubation all tampons sowed the environment for primary crops ofpathological material on a blood tellurite agar.. Accounting of results was carried out in 24 and 48 hours of growth. It is established that the commercial transport liquid medium ofAmes can be usedfor capture of pathological material on diphtheria in the second half of the working day at storage in the conditions of the refrigerator. At the same time, it is necessary to consider a tampon form as the best results on a identification of the causative agent of diphtheria have been received when using a universal tampon.

© 2019, SPb RAACI. Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutinin-activated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy.

© 2018 S. Karger AG.All right reserved. Atypical hemolytic-uremic syndrome is a rare life-threatening disease from the group of thrombotic microangiopathies, caused by the hyperactivation of the complement system. In the most cases it is associated with genetic disorders in the cluster of complement genes. Currently, a large number of different variants of the complement system genes associated with the development of aHUS are described in different countries. In our country, data on the genetic features of pediatric aHUS patients and obstetric aHUS have been published. Genetic changes in the complement system in adult aHUS patients in Russia were not so far presented. Aim: studying the genetic profile of the complement system in adult patients with aHUS. Materials and methods. The study included 20 patients with aHUS: 9 men (45%) and 11 women (55%). All patients underwent molecular-genetic analysis (search for mutations in the clinically significant part of the human genome − exome) by sequencing (Genotek laboratory). Genes CFH, CFHR1-5, CFB, CFI, DGKE, THBD, MCP, C3, С5, ADAMTS13 were analyzed. Results. Genetic variants (mutations) of the complement system associated with aHUS development were detected in 5 patients (25%). Two patients had one mutation, 2 patients − 2 and one patient - 3 mutations. In 3 patients, different genetic variants of the C3 gene were found. Two patients showed the same changes in the CFHR5 gene. In 3 patients, rare changes in the ADAMTS-13 gene, clinically associated with the development of thrombotic thrombocytopenic purpura were found. In all 20 patients, genetic variants of the complement genes with unknown clinical significance were identified, including rare variants of the C3 gene in 9 patients (45%).

© 2018 S. Karger AG.All right reserved. Objective: to estimate the state and the rate of bone metabolism in women with chronic kidney disease (CKD) 1-3 stages during pregnancy. Materialsandmethods:observational cross-sectional and prospective study included 137 pregnant women. CKD 1-3 stage had 85 of them: 64 with CKD 1-2 stage, 21 with CKD 3 stage. Median age 29 years, second and third trimester (42 and 37, respectively). The comparison group consisted of 52 pregnant women with of the same age and gestational age without CKD. Dynamic examination was carried out in 18 cases with CKD 1-3 stage. Ionized, total calcium and inorganic phosphorus, 25-OH vitamin D, parathyroid hormone (PTH), the activity of total alkaline phosphatase (ALP), osteocalcin (OC), N-terminal propeptid of type 1 procollagen (P1NP) and β-isomer of C-terminal telopeptide of type I collagen (β-CTX) were determined. Results: serum calcium, phosphorus and PTH levels in all the examined pregnant women were within their normal range. In pregnant with CKD 3 stage, a deficiency of vitamin D was more significant (р0.02) compared to pregnant women without CKD and pregnant with CKD 1-2 stage. The levels OC and P1NP and β-CTX in pregnant with CKD 3 stage were higher than in the control group and pregnant women with CKD 1-2 stage. It was also higher in pregnant women with CKD 1-3 stages in the third trimester in comparison with the second one, although remained within the limits of reference values. Significant direct correlations were found between serum concentrations of P1NP and OC (r=0.575, р0.001), P1NP and ALP (r=0.415, р=0.001), OC and ALP (r=0.276, р=0, 02) and vitamin D and PTH (r=0.235, р=0.04). A significant inverse correlation was found between the blood levels of vitamin D and P1NP (r=-0.344, р=0.002). Conclusions: the peculiarities of bone metabolism in pregnant with CKD of 3 stage are manifested by the vitamin D deficiency and the acceleration of bone formation and resorption to a greater extent in the third trimester.

© 2018 Nutritec. All Rights Reserved. The article presents modern approaches to dietary support of patients with diabetic nephropathy (DN) characterized by gradual sclerosis of the renal tissue, leading to a loss of filtration and nitrogen excretory function of the kidneys. An analysis of publications of domestic and foreign authors indicates a slowdown in the progression of chronic kidney disease against the background of low-protein diets. However, the role of protein restriction and its qualitative composition in the diet of patients with DN is the subject of comprehensive discussion. KDOQI (2007) Clinical Practice Guidelines and Clinical Practice Guidelines for Kidney Disease determine the target level of protein intake in individuals with diabetes and chronic kidney disease 1-4 stages at the level of 0.8 g/kg of body weight per day. In the recommendations on nutrition for patients with DN, along with a controlled reduction in protein content, great importance is attached to reducing sodium intake from food to 1.5-2.3 gperday. In recent years, close attention has been paid to the use of highly active natural antioxidants for the treatment and prevention of type 2 diabetes, including DN, which was determined by the results of studies demonstrating their beneficial effects on DN patterns. It has been shown that one of the ways to optimize the nutrition of patients with DN is the use of specialized foods modified by protein, fat and carbohydrate composition, including food ingredients with hypoglycemic, hypolipidemic and antioxidant effects.

© 2018 Izdatel'stvo Meditsina. All rights reserved. Aim of the study. To compare the effects of tranexamic acid (TXA), factor XIII concentrate (FXIII) and fibrinogen concentrate on clot formation and fibrinolytic resistance in the in vitro model of hyperfibrinolysis induced by tissue-(tPA) vs urokinase-type (uPA) plasminogen activators. Materials and methods. Citrated whole blood from 28 adult healthy volunteers was supplemented with 10 μg/ mL TXA, 2 lU/mL FXIII, or 3 mg/mL fibrinogen concentrate. Hyperfibrinolysis was induced by spiking the blood with PA or uPA at their half-maximal effective concentrations (90 and 33 lU/mL, respectively). Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry. Results. The use of TXA increased maximal clot firmness in the presence of tPA and markedly inhibited clot lysis in the presence of any of the plasminogen activators. Supplementation of blood with FXIII significantly increased clot firmness and improved fibrinolytic resistance in the presence of either PA or uPA. Supplementation with fibrinogen concentrate elicited a strikingly different effect on clot formation and lysis depending on the type of plasminogen activator. In the presence of tPA, fibrinogen concentrate significantly increased clot firmness and attenuated clot lysis. In contrast, in the presence of uPA, the use of fibrinogen markedly reduced clot firmness and promoted clot lysis. Similar effects of fibrinogen concentrate were observed in platelet-rich and microparticles-free plasma. Conclusion. In hyperfibrinolysis, effect of the hemostatic drugs significantly depends on the type of plasminogen activator used. Therefore, mechanisms of hyperfibrinolysis should be taken into consideration while administering hemostatic drugs.