[Healthy and harmonic childhood - foundation of the «Health of healthy¼ concept]. / Zdorovoe i garmonichnoe detstvo ­ fundament kontseptsii «Zdorov'e zdorovykh¼.

Within the framework of the «Health of Healthy¼ concept (A.N. Razumov) a medical, psychological and pedagogical «Sonatal-pedagogy¼ system (M.L. Lazarev) aimed at harmonizing the mental and physical development of children from the prenatal age has been developed In Russia. The system has been tested since 1983 on population of more than 70 thous. children. The results showed its high effectiveness and safety (in relation to pregnancy, childbirth, breastfeeding, somatic health, psychomotor development and children's abilities). Scaling of the Sonatal-pedagogy, in particular the system of prenatal education, will contribute to the sanitation of the Russian gene pool, demography improvement and formation of responsible parenthood.

[Two models of insulin resistance development and the strategy to combat age-related diseases: literature review].

BACKGROUND: Insulin resistance (IR) is the root cause of most age-related diseases (ARD), the major challenge for today's health systems. Therefore, adequate understanding of the mechanisms underlying IR is essential to build effective ARD prevention. OBJECTIVE: Analyze the existing models of IR causation and progression in order to justify the most effective ARD prevention strategy. METHODS: Search and analysis of publications on IR and hyperinsulinemia (HI) from databases elibrary.ru, PubMed, and Google Scholar. RESULTS: Two models of IR development are analyzed along with the relationship between IR, HI, and obesity. The prevailing model considers obesity (imbalance of caloric intake and energy expenditure) as the main factor in the development of IR; HI is seen as a consequence of IR, mostly insignificant for the outcomes of IR. The model contradicts many experimental and clinical findings. The strategy to combat ARDs that follows from the model (hypocaloric diet and pharmacotherapy of IR) has proven mostly ineffective.The alternative model (IR as a consequence of HI, and obesity as one of IR manifestations) is more consistent with the pool of experimental and clinical data. It more precisely predicts ARD development and allows more adequate correction of adverse lifestyle factors. It corresponds to a different strategy for combating ARD: emphasis on low-carb diet and longer fasting window combined with consideration of other factors of IR. CONCLUSION: If the prevailing model of IR development is revised, this should open up opportunities for more effective early prevention of a wide range of chronic diseases in which the role of IR is significant.

[Hyperinsulinemia and age-related diseases: interrelations and approaches to treatment].

Hyperinsulinemia is closely related with insulin resistance, that is the key mechanism for the progression of age-related diseases. A lot of aspects of hyperinsulinemia and interrelations between the mentioned conditions are very scarcely covered in Russian publications. The present review is designed to fill the gaps in understanding the causal relationships between hyperinsulinemia, insulin resistance, age-related diseases and lifestyle factors. Material and methods. Based on sources from PubMed and Google Scholar, using the keywords "hyperinsulinemia" + "chronic disease" OR "age-related disease" the authors analyzed the causes of hyperinsulinemia, the mechanisms of its influence on various aspects of insulin resistance, and the role of hyperinsulinemia in pathogenesis of a wide range of clinical syndromes and age-related diseases. Consideration of the effects that lifestyle factors produce on hyperinsulinemia opens up opportunities for its correction. Results. The major causes of hyperinslinemia are improper diet and nutrition regime (frequent meals and excess of highly glycemic food, too short fasting window), along with other factors causing hyperreactivity of pancreatic beta-cells (fructose, systemic inflammation, oxidative stress, low vitamin D level, etc.). Hyperinsulinemia affects cellular energy balance (primarily, in liver, muscle, brain and adipose tissue); a major factor is suppression of 5'AMP-activated protein kinase (AMPK) along with stimulation of mitogen-activated protein kinase. Insulin resistance is a consequence of AMPK inhibition, an adaptive response designed to preserve cellular homeostasis. Conclusion. Obesity, metabolic syndrome, chronic systemic inflammation, age-related syndromes and diseases (including arterial hypertension, atherosclerosis, neurodegenerative diseases, tumors, osteoarthritis, sarcopenia, etc.) can be considered as clinical manifestations of the body's systemic adaptation to hyperinsulinemia in the form of insulin resistance. Available approach to reduce insulin resistance is correction of lifestyle factors to mitigate hyperinsulinemia and restore AMPK activity. The revealed causal relationships can provide background for personalized strategy of prevention and treatment for age-related diseases through reduction of insulin resistance and correction of energy homeostasis.

Involvement of the serotoninergic system in the mechanism of action of ultralow dose antibodies to S-100 protein.

The involvement of the serotoninergic system in the realization of anxiolytic and antidepressant activities of antibodies to S-100 protein in ultralow doses is proven. Administration of ultralow-dose antibodies to S-100 protein in combination with serotoninergic agents (ketanserin and 5-hydroxytryptophan) reduced the anxiolytic and antidepressant effects of antibodies.

Study of antidiabetic activity of a new ultralow-dose antibody preparation on the model of streptozotocin diabetes in rats.

Antidiabetic activity of a new ultralow-dose preparation of antibodies to insulin receptor beta-subunit was revealed on the model of streptozotocin diabetes in rats: treatment with this preparation in a daily dose of 2.5 ml/kg (for 50 days through a gastric tube) normalized blood glucose level, restored glucose tolerance in the oral glucose test and body weight gain, and improved animal survival. By its hypoglycemic activity and effect on glucose tolerance the preparation was not inferior to classical drugs for the treatment of types 1 and 2 diabetes mellitus insulin (12 U/kg) and glybenclamide (8 mg/kg).

Comparison of the cardioprotective effects of cardos and losartan in rats with experimental chronic cardiac insufficiency.

Cardioprotective effect of cardos was revealed on rat model of experimental cardiac insufficiency induced by injectionof isoproterenol. Cardos improved exercise tolerance, cardiac output, and stroke volume. Cardos administered for 28 days was no less effective than losartan.

Neuroprotective activity of proproten in rats with experimental local photothrombosis of the prefrontal cortex.

Proproten (ultralow doses of antibodies to S100 protein) exhibited neuroprotective activity in rats with experimental photochemical thrombosis of the prefrontal cortex. Proproten was more potent than standard neuroprotectors piracetam and vinpocetine in alleviating the signs of memory disorders produced by ischemic injury. Pathomorphological study of the damaged area confirmed the neuroprotective effect of Proproten.

A randomized, open-label, comparative, 6-month trial of oral ultra-low doses of antibodies to tumor necrosis factor-alpha and diclofenac in rheumatoid arthritis.

Artrofoon (oral ultra-low doses of antibodies to TNF-alpha is a novel drug approved by the Russian Ministry of Health for the treatment of rheumatoid arthritis (RA). The aim of this study was to assess clinical efficacy and safety of artrofoon in RA compared with diclofenac. In a 6-month, randomized, open-label, comparative trial, 60 patients with active RA (eight men and 52 women aged 23 to 62, mean disease duration 10 years) received artrofoon (8 tablets daily, n = 30) or diclofenac (100 mg daily, n = 30). RA signs and symptoms as well as serum levels of inflammatory markers were evaluated before treatment and at months 1, 3 and 6. Most patients in the artrofoon group showed a 20% improvement in major RA symptoms by the end of the study. The clinical effect rose gradually reaching maximum at month 6. In the artrofoon group, 57% of the patients achieved an American College of Rheumatology (ACR) 20% criteria (ACR20) by month 6 versus 20% of those receiving diclofenac. In some patients in the artrofoon arm, serum proinflammatory cytokine levels significantly decreased (> or = 25% reduction). Diclofenac produced a less pronounced clinical effect, and no changes in cytokine profile. Unlike conventional nonsteroidal anti-inflammatory drugs, artrofoon produced no adverse effects and the overall tolerability and safety were excellent. A half-dose treatment with artrofoon (4 tablets daily) was able to sustain clinical improvements over a 6-month follow-up period. To conclude, artrofoon is a safe and effective treatment for rheumatoid arthritis that acts by influencing the inflammatory process.

Dose-dependent effects and specificity of action of antibodies to endogenous regulators in ultralow doses.

We studied the effects of antibodies against interferon-gamma, erythropoietin, and tumor necrosis factor-alpha in ultralow doses on the production of endogenous interferon-gamma. Course peroral treatment with potentiated antibodies to interferon-gamma in various dilutions produced similar changes in experimental animals. The treatment stimulated spontaneous production of endogenous interferon-gamma by mouse lymphocytes. It should be emphasized that antibodies to other cytokines in ultralow doses did not stimulate interferon-gamma production. These data illustrate the specificity of action of antibodies to endogenous regulators in ultralow doses.