EFFECT OF IMMUNOTHERAPY ACTIVATED T-LYMPHOCYTES ON CELLULAR IMMUNITY IN DIFFERENT FORMS OF ATOPIC DERMATITIS

The article describes the results of therapy with autologous activated. T-lymphocytes in patients with atopic dermatitis. Has been shown high clinical efficacy and safety of this therapy in the treatment of patients with both allergic and nonallergic form of the disease. In the allergic form observed more rapid positive changes, but in the opposite form of the efficiency was higher. Influence on cellular immunity in different forms differed. If the allergic form there was an increase of CD8+ T-cells in the nonallergic form — increased CD8+CD25+ T-cells and changes in delayed-type hypersensitivity

Synthesis of acyclic nucleoside analogues by one-step Vorbrüggen glyco-sylation of 1,2,4-triazolo[1,5-a]pyrimidine-7-ones

New analogues of acyclovir have been prepared by reacting 1,2,4 -triazolo[1,5-a]pyrimidin-7-ones 1а-i and (2-acetoxyethoxy)methyl acetate 2 in the presence of trimethylsilyl trifluoromethanesulfonate as a catalyst. The interaction between the compounds 1а-е and 2 has led to a mixture of N3 and N4 isomers. In contrast, the reaction of compounds 1g-i and 2 proceeded selectively to form N3 isomers. In the case of compounds 1a-c the predominant product is the one with the acyclic moiety in azine ring (N4 isomer). Interaction between 1d-f and 2 has led to mixtures comprising mainly N3 isomer. It has been found that the ratio of glycosylation products 1 and 2 are thermodynamically controlled. The structure of the obtained compounds has been proved by 1Н, 13С, two-dimensional 1Н-13С NMR spectroscopy and X-ray analysis

Non-natural nucleosides based on 1,2,4-triazolo[5,1-c][1,2,4]triazin-4(6H)- ones

Two regioselective methods for the synthesis of nucleosides in the series of 3-phenyl- and 3- ethoxycarbonyl-1,2,4-triazolo[5,1-c][1,2,4]triazin-4-ones were developed. The first route involves a Vorbrüggen glycosylation reaction. The second one is based on condensation of 1,2,4- triazolo[5,1-c][1,2, 4]triazin-4-one sodium salts with protected 1-bromo-sugar derivatives

Formation of a system of target indicators for rating and integral evaluation of the efficiency of the organization of the provision of medical care to patients with diabetes mellitus in the Russian Federation regions

AIM: Formation of a system of target indicators for rating and integral assessment of the effectiveness and efficiency of the organization of medical care for patients with diabetes mellitus in the Russian Federation regions.MATERIALS AND METHODS: The study was an expert survey in the form of a structured interview. At the first stage, we performed the primary selection of indicators. At the second stage, the selection of experts took place in accordance with the inclusion criteria, and the assessment of the level of expert competence was assessed based on a self-assessment survey. Further, criteria we formulated for expert evaluation of the significance of the selected indicators in accordance with the principles used in the development of national and federal projects. The indicators were divided into two groups: additional (process) and main (outcome). To quantify the degree of agreement between the experts’ answers, Kendall’s concordance coefficient (W) was calculated. The significance of differences was assessed using the nonparametric Friedman test.RESULTS: Only indicators with a high degree of agreement between experts and the presence of statistical significance in terms of the concordance coefficient are recommended as target indicators. The following main and additional indicators satisfy these requirements: mortality from cardiovascular complications of type 2 diabetes (people per 100,000 population); the proportion of patients with type 1 and 2 diabetes mellitus provided with medical devices out of the total number of patients with type 1 and 2 diabetes mellitus (percentage); the proportion of patients with type 1 and 2 diabetes mellitus with high amputations of all patients with type 1 and 2 diabetes mellitus with any amputations (percentage); and other indicators.CONCLUSION: We selected indicators that can be used both for the integral rating of the constituent entities of the Russian Federation, and in the formation of federal projects or departmental target programs. The results of the study can also be used to organize a system for monitoring the effectiveness of the implementation of these projects and programs

Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans.Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans

Vaccination of patients with diabetes mellitus

Diabetes mellitus stays an important medical, economic and social problem worldwide. Infectious diseases in people with diabetes mellitus are often more severe with an increased frequency of hospitalizations and complications. The presence of chronic hyperglycemia leads to decreased immune function and an increased predisposition to infections. Infections lead to uncontrolled hyperglycemia, which worsens the course of infections, thus forming a vicious circle of violations.Mass vaccination with an emphasis on people belonging to the high-risk group reduces the number of infected and, hospitalized people, and also has clear economic advantages. However, in many countries the proportion of vaccinated remains low.Vaccine prophylaxis in Russia is regulated by a number of regulatory legal acts, of which the main one is Federal Law No. 157-FZ of September 17, 1998 (edited on July 2, 2021) «About Immunoprophylaxis of Infectious Diseases». Each country has a National Vaccination Schedule, which shows a routine vaccination schedule at a specific age against infections that are widespread and / or pose a serious threat to health and life), as well as a National Epidemic Indication Vaccination Schedule. In Russia, these documents are approved by Order of the Ministry of Health of the Russian Federation of March 21, 2014 N 125n «About the approval of the national calendar of preventive vaccinations and the calendar of preventive vaccinations for epidemic indications.»This article discusses vaccination against the most socially significant infections associated with a high worldwide prevalence and increased risk among people with diabetes

COVID-19 and kidneys

COVID-19 poses a real threat to patients with comorbid conditions such as diabetes mellitus (DM), hypertension, cardiovascular, renal or hepatic disorders. Kidney damage is very likely in people with diabetes who have undergone a new infection, and the risk of developing acute renal injury is associated with mortality. Potential mechanisms of kidney involvement in the clinical picture of the disease may include cytokine damage, cross-organ damage, and systemic effects that determine the treatment strategy. These mechanisms are closely interrelated and are important for individuals on extracorporeal therapy and kidney transplants. Autopsy data provide evidence of SARS-CoV-2 virus invasion into kidney tissue with damage to tubular epithelium cells and podocytes, and red blood cell aggregation in severely COVID-19 patients. By including individuals with chronic kidney disease in planned COVID-19 research protocols, an evidence base for effective and safe treatments can be generated

Pathogenetic mechanisms regulating trigeminal nociceptive system in migraine

Trigeminal somatosensory evoked potentials (TSEPs), thyroid-stimulating hormone (TSH) and quality of life (QoL) were studied in 123 migraine patients and 10 healthy subjects. Latency of P1 as well as asymmetries of P1 latency and N1P1 amplitude were enlarged in migraine patients. Lower levels of TSH in migraine patients correlated with more pronounced asymmetries in TSEPs and poor QoL. Conclusion: TSH levels may play role in modulation of trigeminal system in migraine.Исследованы тригеминальные соматосенсорные вызванные потенциалы (ТССВП), уровни тиреотропного гормона (ТТГ) и показатели качества жизни (КЖ) у 123 пациентов, страдающих мигренью, и 10 здоровых лиц соответствующего возраста. Выявлено увеличение латентности N1, Р1 и N2 и нарастание асимметрий латентности Р1 и амплитуды N1P1 ТССВП по сравнению с контрольной группой. Более низкие уровни ТТГ у больных мигренью ассоциировались с более выраженной асимметрией показателей ТССВП и более низким качеством жизни, что может свидетельствовать о возможном участии гормональной оси гипофиз - щитовидная железа в модуляции тригеминальной системы при мигрени

Time in range is a tool for assessing the quality of glycemic control in diabetes

The presence of continuous glucose monitoring (CGM) systems has expanded diagnostic capabilities. The implementation of this technology into clinical practice allowed to determine the patterns and tendencies of excursions in glucose levels, to obtain reliable data concerning short-term glycemic control. Taking into consideration the large amount of obtained information using CGM systems, more than 30 different indicators characterizing glycemic variability were proposed. However, it is very difficult for a practitioner to interpret the data obtained due to the variety of indicators and the lack of their target values. The first step in the standardization of indices was the creation of the International Guidelines for CGM in 2017, where the Time in Range (TIR) (3,9–10,0 mmol/l, less often 3,9–7,8 mmol/l) was significant. To complement the agreed parameters and simplify the interpretation of obtained data using CGM, in 2019 the recommendations were prepared for the International Consensus on Time in Range, where TIR was validated as an additional component of the assessment of glycemic control along with HbA1c. In the literature review the issues of the association of TIR with the development of micro- and macrovascular complications in type 1 and 2 diabetes are considered. The relationship with other indicators of the glycemic control assessment was also analyzed and the dependence of insulin therapy on TIR was shown. TIR is a simple and convenient indicator, it has a proven link with micro- and macrovascular complications of diabetes and can be recommended as a new tool for assessing the glycemic control. The main disadvantage of TIR usage is the insufficient apply of CGM technology by the majority of patients with diabetes

Experience of long-term use of anti-IgE therapy in a patient with chronic spontaneous urticarial

Chronic spontaneous urticaria is an urgent health problem. Recurrent urticarial rashes, angioedema and severe itching reduce the quality of life of patients. The ineffectiveness of standard therapy requires the search for new modern methods of treating this disease. Taking into account the current data on the pathogenesis, the third line of therapy for chronic spontaneous urticaria is the addition of anti-IgE therapy (omalizumab) to antihistamines of the 2nd generation. The presented clinical case is devoted to the experience of long-term use of omalizumab in a patient with chronic spontaneous urticaria. Having a disease duration of about a year, the patient was thoroughly examined, all concomitant diseases were identified and compensated, parasitic invasion was treated, but this did not lead to a regression of symptoms. Antihistamines of the 2nd generation in standard and increased doses (up to 4 times) did not control the disease, systemic glucocorticosteroids stopped the symptoms for a short time, and therefore, in  the future, the  patient began to use them independently and uncontrollably. Almost daily use of  corticosteroids for 6 months caused the development of complications in the form of weight gain and Cushing’s syndrome. Omalizumab completely stopped all the symptoms during the first day, no side effects were detected. The clinical effect lasted from 3 to 4 weeks. Thus, omalizumab therapy allowed the patient to almost completely get rid of the symptoms of CSC, which significantly improved the quality of life and made it possible to cancel systemic glucocorticosteroids. The peculiarity of the presented case is the duration of the use of omalizumab (more than 2 years) with the inability to cancel due to the return of urticarial rashes and itching