No abstract

Since 2010, Russia has been developing new drug legislation, internal quality control and safety of medical organizations, and has developed algorithms for submitting Individual Case Safety Reports (ICSR) using an automated information system. On April 1, 2019, Russia launched an updated national database of ICSR, which uses the international ICH E2B data standard, which may increase the amount of reporting to the Uppsala monitoring center. This publication covers the key aspects of pharmacovigilance system development in the Russian Federation. The analysis of pharmacovigilance structure in the Russian Federation is carried  out, its main problems are designated. Presents methods to identify causal relationships between adverse reaction and drug, evaluation of its degree of validity (questionnaires, algorithms, and scale), as already recommended by the WHO, and the new modifi ed versions. The expediency of using a scale for determining the degree of reliability of a causal relationship «an undesirable reaction — drug interaction» when analyzing spontaneous reports of undesirable reactions that may be caused by drug interactions is noted. An effective method of detection and prevention of adverse reactions is presented — the Global Trigger Tool (GTT). The question of the need for motivation and training of medical personnel in the correct design of spontaneous messages, as well as methods of identifying the causal relationship between adverse reactions of drugs. The directions of optimization of pharmacovigilance system are proposed, including methods of more effective active surveillance in the identifi cation and prevention of adverse reactions.

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

The paper provides current data on some proteins of the TGF- p family which are potentially capable of exerting a protective effect in diseases of the heart, lungs, placenta, gonads, and pancreas. The study investigated the anti-inflammatory properties of follistatin-like protein-1 (FSTL-1), one of the proteins of this family, at the cellular level. It was demonstrated that FSTL-1 is responsible for heart muscle regeneration in mammals through activation of angiogenic factors. Despite the fact that this protein plays a key role in myocardial regeneration, its concentration in the epicardium decreases immediately after a heart attack, which hampers effective self-repair of the heart. The paper summarises the results of studies of the efficacy of intravenous administration of FSTL-1 in rats with myocardial infarction. However, the administration of a foreign protein can cause allergic reactions, therefore a drug that induces FSTL-1 secretion was chosen instead.The aim of the study was to provide experimental substantiation of the possibility of exogenous regulation of FSTL-1 secretion.Materials and methods: FSTL-1 concentration in rat plasma was assessed by enzyme immunoassay before and after treatment with the antioxidant drug ethyl methyl hydroxypyridine malate. The antioxidant was administered to 15 healthy male Wistar rats subcutaneously 3 times a day at a dose of 6 mg/day for 14 days. A fasting blood sample was obtained on the first day before administration of the drug and on day 15.Results: after the period of treatment with ethyl methyl hydroxypyridine malate the concentration of FSTL-1 in the plasma of the laboratory rats increased significantly (p = 0.0011) to reach 0.92 ± 0.11 ng/mL as compared to the initial concentration of 0.48 ± 0.04 ng/mL.Conclusion: the study provided experimental evidence for new properties of ethyl methyl hydroxypyridine malate, i.e. induction of FSTL-1 in healthy rats. Further studies are encouraged to assess potential use of this drug as an inductor of FSTL-1 in myocardial ischemia.