[Novel Possibilities in Pharmacotherapy of Patients With Chronic Heart Failure].

In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril. Advantages of the use of valsartan + sacubitril for the budget were demonstrated in pharmacoeconomic studies. These advantages are maximally realized at long-term administration. Cost-efficacy of the use of valsartan+sacubitril in pharmacotherapy of CHF is comparable with that of statins in the treatment of ischemic heart disease or implantation of a cardioverter-defibrillator in prevention of sudden cardiac death. Thus, introduction of the drug into practice can be expected to reduce budget expenditures.

[Carboxytherapy - an innovative trend in resort medicine]. / Karboksiterapiia - odno iz innovatsionnykh napravlenii v kurortologii.

Carboxytherapy (the treatment based on carbon dioxide injections) is a multipurpose and widely used medical technology. The use of CO2 injections (intracutaneous, subcutaneous, and pneumopuncture) have substantially supplemented and increased the practical relevance of carboxytherapy as a method for the treatment of many diseases. Thanks to it physiological properties, CO2 has antihypoxic, antioxidant, vasodilatory, anti-inflammatory, analgesic, and spasmolytic activities; moreover, it improves blood viscosity, stimulates neoangiogenesis, and regenerative processes. Carbon dioxide is a sort of biochemical 'peacemaker' in tissue oxygenation: when blood cells are exposed to high CO2 concentrations (Bohr effect), the rate of gas exchange (CO2 and O2) increases. The human organism interprets carboxytherapy (local hypercapnia) as oxygen deficiency and responses to it by boosting not only the blood flow, but also the vascular endothelial growth factor which stimulates neoangiogenesis and in the long run improves blood supply and tissue trophism. The multiple mechanisms of action, polymodal efficacy, a tool kit with a wide range of detectors and various modes of treatment make carboxytherapy a popular medical technology all over the world, namely in cosmetology, dermatology, aesthetic medicine, angiology, orthopaedics, cardiology, neurology, pulmonology, gynaecology, urology, proctology, plastic and general surgery, and other areas. Carboxytherapy provides a perfect example of the off-label usage in medicine that made it one of the most extensively applied medical technology for the treatment of various diseases despite the lack of the preclinical data and scarce relevant information available in textbooks, reference books and booklets.

[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].

Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.

[COMORBIDITY AND POLYMORBIDITY IN ADULTS AND CHILDREN IN THE LIGHT OF THE PROBLEM OF NSAID-GASTROPATHY].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most demanded drugs. Paper presents the data review on the drug activity mechanisms, effectiveness, safety, and major drug interactions of NSAIDs at co-morbid conditions in different age groups, as well as measures of prevention of NSAID-gastropathy, which can occur even against the use of small doses of NSAIDs. The existing recommendations on the selection of NSAIDs and the complex therapy with drugs of this pharmacological group are shown in considering the individual characteristics of the patient, the pharmacological properties of drugs, the clinical picture of the disease, the presence of risk factors for adverse reactions and drug interactions.

[THE FEATURES OF SECRETION AND STOMACH MOTOR PROCESSES IN PATIENTS WITH DUODENAL ULCERS AS A CAUSE FOR REDUCING BIOAVAILABILITY OF PROTON PUMP INHIBITORS].

UNLABELLED: The article contains the modern data about the role of duodenal reflux in the development of acid-dependent diseases of stomach and duodenum. There are the results of studies in which the known quantitative parameters of duodenal reflux in the duodenal ulcer patients were simulated to identify their influence on the disintegration of enterosoluble dosage forms and the bioavailability of proton pump inhibitors (in healthy volunteers, patients with gasritis, exacerbation and remission of peptic ulcer disease the pharmacokinetics of lansoprazole, intragastric pH-metry with floating capsule for teleradio-pH-metry were investigated, and in an in vitro study the dissolution tests of proton pump inhibitors with pH 3 and pH = 4 were made). CONCLUSION: The high-amplitude oscillations of intragastric pH, observed during exacerbation of duodenal ulcer, can lead to an early disintegration of enteric-coated dosage form of proton pump inhibitors in the stomach, its destruction and decreased bioavailability.

[The efficacy of ethylmethylhydroxypyridine in the rehabilitation treatment of poststroke patients]. / Effektivnost' primeneniya etilmetilgidroksipiridina suktsinata v vosstanovitel'nom lechenii patsientov, perenesshikh ishemicheskii insul't.

The analysis of the clinical efficacy and safety of ethylmethylhydroxypyridine succinate (mexidol) in the complex of rehabilitation measures in patients after ischemic stroke (IS) shows that course treatment with mexidol improves the recovery of neurological functions, decreases neurological deficit, cognitive disorders, including memory impairment, and manifestations of asthenic syndrome, increases the level of social adaptation and improves the psycho-emotional state of patients, reduces spasticity, increases motor and speech activity, praxis, reliably eliminates the ignoring syndrome. There is a decrease in the level of total cholesterol and low-density b-lipoproteins in the blood, and decrease in the severity of hypercoagulation. The results of the studies have convincingly shown the efficacy of mexidol at all stages of rehabilitation treatment of patients with IS.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s khronicheskoi ishemiei golovnogo mozga.

Chronic cerebral ischemia (CCI) is a common cerebrovascular syndrome, the development of which is associated with a high risk of increasing cognitive, behavioral, and motor disorders, and the formation of a patient's dependence on others. Timely start of treatment can slow down the course of the disease, make it more favorable. The review considers the possibility of using the domestic neuroprotector mexidol in patients with CCI. The results of a series of clinical studies on the use of ethylmethylhydroxypyridine succinate (mexidol) in patients with CCI are analyzed. The effectiveness of the drug in relieving cognitive, affective and motor disorders is noted. Information about the good tolerance of mexidol is presented.

[Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke]. / Effektivnost' i bezopasnost' primeneniya etilmetilgidroksipiridina suktsinata u patsientov s ostrym ishemicheskim insul'tom.

Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it's important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile.

[Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL-1) in myocardium after experimental infarction in rats]. / Issledovanie vliianiia étoksidola na ékspressiiu follistatin-podobnogo belka-1 (FSTL-1) v miokarde posle éksperimental'nogo infarkta.

In heart attack, FSTL-1 is actively secreted by cardiomyocytes, accelerates growth of heart myofibrils and stimulates of vascular endothelial growth factor expression. The aim of this work was to investigate the effect of Etoxidol on synthesis of FSTL-1 in rats after myocardial infarction. The experiments were performed on Wistar rats weighing 250-350 g with simulated myocardial infarction or intact (group 5). Animals of control groups (groups 1, 2) were treated with saline for 7 and 14 days; Ethoxidol (24 mg/kg) was injected to animals of experimental groups (group 3, 4) (the daily dose was 6.36 mg/animal) for 6 or 14 days. The injection volume was 0.2 ml. At the beginning and at the end of the study plasma concentrations of FSTL-1 were determined by the ELISA method. Myocardial FSTL-1 gene expression was determined by real-time PCR. At the end of the experiments, the hearts were also used for histochemical analysis. To determine the size of the scar formed after the modeled heart attack, we used the classic Mallory staining method. The results show that the development of experimental acute myocardial infarction is accompanied by a significant increase in FSTL-1 expression in the heart, which was detected on the 7th day and stored increased by 14 days after a heart attack. After therapy with Ethoxidol, a tendency to a decrease in the expression of FSTL-1 by the 14th day was observed; it coincided with the dynamics of the plasma protein FSTL-1 level. It can be assumed that the downregulation trend in the FSTL-1 expression is associated with a more effective repair process after a heart attack, since FSTL-1 increases precisely in response to myocardial damage and decreases when the incentives for its expression from damaged heart tissue are reduced. Indirectly, this assumption is confirmed by the detected tendency to reduce the size of post-infarction fibrosis in the treatment with Ethoxidol. The results indicate the ability of Ethoxidol to influence FSTL-1 synthesis of in rats after myocardial infarction.

The Mechanism of Action of Ethoxidol on Oxidative Stress Indices in Heart Failure and Hypotension.

The aim of the investigation was to study the effect of 2-ethyl-6-methyl-3-hydroxypyridine malate (Ethoxidol) on the concentration of oxidative stress metabolites in patients with chronic heart failure (CHF) and hypertension. MATERIALS AND METHODS: 126 patients with FC I-III CHF have been examined. In addition to their individual therapy these patients received intravenous infusions of Ethoxidol. Blood content of 2,3-diphosphoglycerate (2,3-DPG), oxygen tension (рО2), pH, concentration of total peroxides, lactate, and aldosterone were identified. 2,3-DPG levels (g/L erythrocytes) in whole blood samples were determined by an enzyme assay using the reagent kit (Rosh, Germany), values of рО2, рСО2, рН, lactate in the venous blood were measured using gas analyzer Stat Profil pHOx Ultra (Nova Biomedical, USA). Indices of oxidative stress, i.e. the concentration of plasma total peroxides, were investigated by ELISA using OxyStat kit (Biomedica, Austria). Peripheral venous blood samples were collected from all patients before and 6 days after the daily intravenous Ethoxidol infusion. RESULTS: In patients with FC I, II, III CHF, on day 7 after intravenous Ethoxidol infusion at a dose of 100 mg/day, statistically significant growth (p=0.0002) of PaO2 level by 15.7, 17.4, and 22.8%, respectively, was noted. In patients with FC I, II, III CHF in the group receiving standard therapy, statistically significant (p=0.002) reduction of 2,3-DPG level by 2.7, 2.4, and 4.0%, respectively, was registered. On day 7 after the infusion of Ethoxidol at a dose of 100 mg/day, its decrease by 5.7, 10.5, and 26.2%, respectively (p<0.0001), was also observed. CONCLUSION: The increased concentrations of active oxygen forms have been established to negatively affect various bodily functions and adversely influence the pathophysiology of numerous diseases. Application of antioxidants, including Ethoxidol presented by us in this article, may become a clue to the development of preventive measures for many serious diseases.

[Contemporary aspects of aviation ophthalmic ergonomics]. / Sevremennye aspekty aviatsionnoi oftal'moérgonomiki.

The article tackle problems of ophthalmic ergonomics in contemporary aviation. The authors necessitate PC software to be put into practice of medical examination in pilots, stress efficacy of photorefraction surgery for vision rehabilitation and better occupational adequacy of pilots.