Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. There is a pressing clinical need for advanced colon-specific local drug delivery systems that can provide major advantages in treating diseases associated with the colon, such as inflammatory bowel disease (IBD) and colon cancer. A precise colon targeted drug delivery platform is expected to reduce drug side effects and increase the therapeutic response at the intended disease site locally. In this study, we report the fabrication of hyaluronan (HA) functionalized polymeric hybrid nanoparticulate system (Cur-HA NPs) by using curcumin as a model fluorescent drug. The Cur-HA NPs were about 200–300 nm in size, −51.3 mV overall surface charge after HA functionalization, with 56.0% drug released after 72 h in simulated gastrointestinal fluids. The Cur-HA NPs did not exhibit any cytotoxicity by AlamarBlue, PicoGreen and Live/Dead assays. Following the Cur-HA NPs use on HT-29 monolayer cell cultures demonstrating, the efficacy of HA functionalization increases cellular interaction, uptake when compared to uncoated nanoparticulate system. These findings indicate that HA functionalized nano-hybrid particles are effective in delivering drugs orally to the lower gastrointestinal tract (GIT) in order to treat local colonic diseases.

© 2018, Pediatria Ltd. All rights reserved. The article presents results of conjugated pneumococcal vaccine use in combination with basic therapy in 64 children with chronic compensated tonsillitis. The study showed that vaccination assists activation of T-lymphocytes subpopulation, increases sensitization to bacterial antigens, normalization of proinflammatory cytokines content, which is clinically manifested in a significant decrease in acute respiratory infections incidences and antibacterial therapy courses for 2 years after vaccination compared to patients receiving a traditional therapy course.

© 2017 Elsevier Masson SAS A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11–18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Infections are the main cause of death for patients with autoimmune rheumatic diseases. In adult patients with rheumatoid arthritis (RA), mortality caused by respiratory infections is 2-5 times higher than in the population. One of the frequent infectious complications in the course of treatment with tocilizumab, the first-choice drug for treating systemic juvenile idiopathic arthritis (sJIA), is pneumonia characterized by a poor clinical picture, normal values of laboratory indices of the disease activity (ESR, C-reactive protein) with pronounced changes in the lungs revealed by computed tomography. In case of acute respiratory infection in children with systemic JIA, immunosuppressants and genetically engineered biological preparations (GEBP) are discontinued. This often leads to an exacerbation of the underlying disease and the progression of a pathological process. At present, vaccination against pneumococcal infection in Russia is not included in the standard for managing patients with rheumatic diseases. Studies of the safety and efficacy of vaccination with 13-valent pneumococcal conjugate vaccine (PCV) in patients with sJIA receiving genetically engineered biological preparations were not conducted. Clinical Case Description. The article shares the experience of vaccination of a girl aged 9 years with a 13-valent PCV that was conducted in the course of a scientific investigation, which studied the efficacy and safety of vaccination of children with systemic JIA prior to prescription of GEBP tocilizumab. Vaccination did not cause a deterioration in the course of the main disease (1 month), led to a reduction in the incidence of acute respiratory infections (from 4 to 1 time within 6 months before and after vaccination), and discontinuation of antibacterial drugs within 6 months after vaccination. Conclusion. The safety of a 13-valent PCV in a child with sJIA and a decrease of the incidence of respiratory diseases after vaccination, their complications, and the use of antibacterial drugs have been shown.

© 2018. Conjugates of Streptococcus pneumoniae type 9N capsular polysaccharide with tetanus toxoid have been prepared. Their interactions with specific antibodies to tetanus toxoid and polysaccharide 9N were assessed, which permitted to select a conjugate with the optimal ratio of the polysaccharide and carrier protein (3:4). The parameters of the efficient adsorption of tetanus toxoid and polysaccharide on aluminum hydroxide for the following in vivo experiments were determined using the quantitative ELISA; in particular, the optimum ratio of the conjugate and adjuvant was proved be ≤ 1:1 (w/w). The repetitive immunization with the selected conjugate adsorbed on aluminum hydroxide increased the anti-PS antibody titers up to 70400 (p < 0,001) which is 140-fold higher as compared to the antigen unconjugated form. The investigation of the antibody protection from Streptococcus pneumoniae 9N after the intranasal challenge of wild-type mice revealed that the titer of the bacterial contamination in the immunized mouse lung tissue was 10-fold lower than that in non-immune mice 72 h after the contamination (p > 0,05).

© 2018 Medical Education. All rights reserved. The aim of this study was to assess long-term effects of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) and 13-valent conjugate vaccine (PCV13) in patients with bronchial asthma. Methods. One hundred and three patients with mild to severe asthma were involved. They were randomly assigned to vaccination with PCV13, or PPV23, or PPV23 followed by PCV13, or vice versa. Clinical efficacy of vaccination was evaluated using number of asthma exacerbation a year before and 1 and 4 years after the vaccination; need in antibiotics a year before and 1 and 4 years after the vaccination; and number of hospitalizations due to asthma exacerbation a year before and 1 and 4 years after the vaccination. Results. In a year after vaccination, number of patients who had not experienced asthma exacerbation increased significantly in PPV23, PPV23/PCV13, and PCV13/PPV23 groups (p < 0.01 to p < 0.001). In 4 years after vaccination, number of patients without exacerbations increased significantly in PCV13/PPV23 group only (48.1%; p < 0.01). Number of patients who did not require hospitalization due to asthma exacerbation increased significantly in PCV13 group only (81.8%; p < 0.05). Conclusion. The authors proposed a hypothesis of impact of pneumococcal vaccines on immunopathogenesis of bronchial asthma. The authors consider vaccination against pneumococcus using PCV13 followed by PPV23 should be a part of the basic therapy of asthma.

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved. Vaccination against pneumococcal infections by 13-va-lent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality. The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection. Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system. The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level. In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given. The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018. Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided. Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively). In the 15-year-horizon noting the distribution of 65-year-olds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively. Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.