The redox transformations and nucleophilic replacements as possible metabolic reactions of the drug “Triazaverin”. The chemical modeling of the metabolic processes

As a model of metabolic transformations of antiviral drug “Triazaverin” and its analogues‑2-alkylthio‑6-nitro‑1,2,4-triazolo[5,1-c][1,2,4]triazine‑7-ones 1a-d examined the oxidation of alkylthio groups to the corresponding sulfoxides 2a-d and sulfones 3a-d, as well as the process of nucleophilic substitution sulfonyloxy group of cysteine and cysteamine with the formation of compounds 5 and 6

Impact of technological blockchain paradigm on the movement of intellectual property in the digital space

The article is dedicated to investigate the problem of influence of cutting edge digital technology on the virtual and real legal relations, related to the movement and the turnover of intellectual property. Using the method of analyzing modern definitions of blockchain, and relying on the political-economic theory of social redistribution of wealth, authors define the term blockchain and its principles as a technological paradigm. Authors conclude the fact that blockchain can be used to guarantee intellectual property rights and it should be accepted at the national level. As a mechanism of a trusted environment, blockchain allows to reduce transaction costs and increase the level of commercialization of intellectual property.peer-reviewe

Application of modern immunological methods in the diagnosis of tuberculosis in HIV-infected patients

Combination of TB and HIV-infection is still the most nowadays important problem, and it connects not only with steady growth of HIV infection, but with difficulties in TB diagnosis. X-ray lung studies often have unusual nature, clinical symptomatology appears when process are hard and spread. At the same time in global practice IGRAtests applying, to which they belong to SPOT.TB test and QuantiFERON®-TB Gold test, they pay great attention to it, particularly among patients with HIV- infection. In study there were data when 41 patients with lung TB were examined, 56 HIV-positive patients with lung TB and 58 healthy donors. When active TB IGRA-test and test with Diaskin test show comparable same results. Against the backdrop of HIV skin tests (Mantoux test with 2 TE and tests with Diaskin test) it was demonstrated direct dependence of level immunosuppression in contrast to IGRA – tests, that allows to carry out these researches in conditions when standard skin tests do not work

ECONOMIC BENEFITS OF LEFT VENTRICULAR HYPERTROPHY REGRESSION IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To evaluate by modelling the economic benefits of left ventricular hypertrophy (LVH) regression in patients with arterial hypertension (HT) due to therapy with fixed combination of valsartan/amlodipine.  Material and methods. 20 patients (15 females and 5 males, aged 18 to 70 years) with essential HT accompanied by metabolic syndrome with a history of previous ineffective antihypertensive therapy were included into the study. All patients were treated with fixed combination of amlodipine/valsartan in doses of 5/160 and 10/160 mg depending on blood pressure (BP) level. Treatment duration was 24 weeks. Changes in BP level, LVH regression were assessed. Economic evaluation was performed on the basis of modelling with the specialized software Decision Tree 4.xla. Results. Effect of fixed amlodipine/valsartan combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to left ventricular (LV) mass (at baseline and after 24 weeks of therapy). Significant decrease in LV mass from 205.8±50.4 to 181.9±45.1 g (p<0.05) was revealed. The model took into account economic and frequency factors for 10 year prognosis: this therapy prevents 36 deaths, 6 strokes, 24 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save 2 516 772.42 RUR for every 1 000 patients. It would reduce the total costs per patient during 10 years. Conclusion. Treatment with amlodipine/valsartan single pill combination has not only clinical advantages, but also pharmacoeconomic benefits. This combination reduces risk of acute myocardial infarction and death more effectively. Treatment with fixed valsartan/amlodipine combination saves maximum years of life with less cost during 10 years. Despite of higher pharmacotherapy costs, fixed valsartan/amlodipine combination reduces total costs due to prevention of fatal and nonfatal cardiovascular events

Azoloazines as Perspective Antiglycating Agents for Therapy of Diabetes Complications

This work was supported by Russian Federation Ministry of education and science (grant № 4.6351.2017/8.9) and Russian Foundation for Basic Research (grant № 18-03-00787)

TREATMENT EFFICIENCY OF DRUG SUSCEPTIBLE PULMONARY TUBERCULOSIS

The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-О,N’) ferrous dihydrate sulphate (II) and isoniazid in drug susceptible pulmonary tuberculosis patients.The high treatment efficiency namely significant improvement and improvement was observed in the patients of Group 1 – 84.1% which could be compared to the standard treatment regimen (85-7%) in Group 2. The total number of adverse reactions in the main group was confidently lower – 18.6% against 33.9%, p < 0.05. Hepatotoxic reactions with 2-3 fold increase of alaninetransferase level was registered significantly less (9.3%) in Group 1 compared to the Group treated with isoniazid

Therapy of Schizoaffective Disorder and Paranoid Schizophrenia with Episodic Course

Background. The use of atypical antipsychotics in schizophrenia contributes to the reduction of psychotic, affective, negative and cognitive disorders.Aims. To evaluate the effectiveness of ziprasidone therapy in patients with schizoaffective disorder and paranoid schizophrenia with episodic course.Materials and methods. In accordance with ICD-10 there were 14 (63.6 %) people with schizoaffective disorder (F25), 8 (36.4 %) people with paranoid schizophrenia, episodic course (F20.x1). Treatment with ziprasidone lasted 42 days. The dose of ziprasidone in 6 patients (27.3 %) was 80 mg, in 10 patients (45.5 %) – 120 mg, in 6 patients (27.3 %) – 160 mg. Evaluation of the effectiveness of ziprasidone therapy was carried out using psychometric scales (PANSS, General clinical impression scale to assess the effectiveness of therapy – CGI-S, CGI-I), adverse events were registered with the UKU scale.Results. The number of respondents was 19 (86.3 %) (reduction of the total score on the PANSS scale > 20 % of the pre-treatment level). Ziprasidone was effective in patients with schizoaffective disorder with a significant decrease in total score on PANSS subscales to the 14 th day of therapy (p < 0.05), with paranoid schizophrenia with episodic course – by the 21st day (p < 0.01). According to the CGI-S scale at the end of therapy, “borderline condition” was observed in 10 patients (52.6 %), mild severity – in 3 (15.8 %), normal condition – in 6 (31.6 %). CGI-I scale showed a significant improvement in 10 patients (52.6 %), marked improvement – in 9 patients (47.4 %). Among the mild adverse events that do not require discontinuation of the drug, we noted: weakness – in 3 patients (15.8 %), drowsiness – in 3 (15.8 %), impaired concentration – in 2 (10.5 %), orthostatic dizziness – in 2 (10.5 %), galactorrhea – in 1 (5.3 %).Conclusions. Ziprasidone is an effective antipsychotic drug that has a safe tolerability profile. It can be used in patients with schizoaffective disorders and paranoid schizophrenia with episodic course

Nucleophilic substitution of nitro group in nitrotriazolotriazines as a model of potential interaction with cysteine-containing proteins

[Figure not available: see fulltext.] The nucleophilic susbstitution of nitro group in [1,2,4]triazolo[5,1-c][1,2,4]triazinones upon treatment with cysteine and glutathione was studied as a model for the interaction with thiol groups of virus proteins, which mimics the metabolic transformations of antiviral drug Triazavirin® and its derivatives. © 2015 Springer Science+Business Media New York.Russian Science Foundation, RSF: 14-13-01301The study was performed with the financial support from the Russian Science Foundation (grant 14-13-01301)

DIAGNOSTIC VALUE OF SPECIFIC IMMUNE COMPLEXES IN DETECTION OF ACTIVE TUBERCULOSIS INFECTION

The diagnostic of tuberculosis infection, including the use of immunological methods, evolved significant changes. The introduction of new diagnostic tests allowed to improve the diagnosis of latent tuberculosis infection (LTI). However, the positive results of immunological tests in both tuberculosis patients and in those with LTI do not allow to divide these conditions, which requires the development and implementation of new diagnostic approaches.Materials and methods. A prospective study with a survey of two groups of patients was conducted: group I (n=50) - patients with verified pulmonary tuberculosis, MBT (+); group II (n =15) – subjects with LTI and control group – healthy subjects (n=14). The examination complex included clinical, radiological, bacteriological, immunological (Mantoux test with 2 TU, T-SPOT.TB, QFT and Diaskintest) methods. Immune complexes were determined in all patients and healthy individuals by the method of dynamic light scattering after the in vitro addition of specific antigens - peptides ESAT-6 and SFP-10.Results. The obtained data demonstrate the low informativeness of the clinical method in the diagnostic of pulmonary tuberculosis. In the presence of characteristic X-ray changes, bacteriological verification of tuberculosis was obtained only in 46% of cases. The use of various immunological tests allows to obtain positive test results in 84-90% of cases simultaneously with the 100% of the positive results in subjects with LTI. Determination of specific immune complexes by the method of dynamic light scattering allows to determine the activity of tuberculosis infection in 100 % of cases and to identify a high-risk group for the development of active tuberculosis in people with latent tuberculosis infection.Conclusions: the obtained data can be applied not only in the diagnosis of active tuberculosis in the absence of diagnosis verification, but also allow to identify a high-risk group for the development of the disease in people with latent tuberculosis infection