A new approach to the treatment of the Type 2 diabetes mellitus (T2DM) based on drug-induced glycosuria and reduction in renal threshold of glucose, and drugs with a similar mechanism of action belong to an innovative class of antidiabetic drugs: inhibitors of 2nd type sodium-glucose cotransporter (GLT-2). In addition to improving glycemic control SGCT-2 inhibitors promote moderate weight loss and blood pressure (BP), increased sensitivity of tissues to insulin and improve β-cell function. Dapagliflozin an oral SGCT-2 inhibitor, which is due to the insulin independent mechanism of action is characterized by the minimal risk of hypoglycemia compared to traditional antidiabetic drugs, such as sulfonylurea and insulin. For this reason, the drug has the unique ability to combine with other oral hypoglycemic agents (OHGA). In addition, due to its natriuretic effect and ability to reduce body weight and blood pressure dapagliflozin is the drug of choice in patients with T2DM and cardiovascular diseases of atherosclerotic genesis. A combination of advantages, including a favorable safety profile of dapagliflozin allows extensive use of this drug for the initiation and intensification of T2DM treatment.

BACKGROUND: Biologically active regulatory peptides are the drugs of new type that act selectively on targets, with having no significant side effects. AIM: The aim of the study was to study the potential effect of peptide preparations Cortexin and Semax on the resistance of the rat organism to the cold stress factor in the model of cold stress maladaptation. MATERIALS AND METHODS: White outbred male rats were injected intraperitoneally twice daily with placebo (n = 30), Cortexin 5 mg/kg (n = 30) or Semax 0.3 mg/kg (n = 30). Three days after the start of the injection course, the cold-stress effect was simulated in the climate chamber (Feutron, Germany) by cooling the air to 5C at a relative humidity of 7580%. RESULTS: The use of RP significantly increased the duration of the rectal temperature plateau-period within 35C (moderate hypothermia): in animals of the Cortexin group from 10 days to 12 days, and in animals of the Semax group, from 10 to 14 days. Cortexin demonstrated moderate immunomodulatory properties, and Semax had a more pronounced immunomodulatory effect. Both preparations showed a stress-protective effect. The use of regulatory peptides provided to delay the decrease in the rat general motor activity and exploratory behavior which develops under the influence of a simulated cold-stress factor. A slower rate of decrease in the swimming time of rats under the influence of regulatory peptides was registrated. CONCLUSIONS: The meteoadaptogenic, stress-protective and nootropic effects of the regulatory peptides Cortexin and Semax were confirmed in rats on the model of cold-stress maladaptation.

The article discusses the pathophysiological mechanisms of the development of vascular aging as a combination of the influence on the  body of  genetic, environmental, regulatory, metabolic and other factors causing biochemical, enzymatic and cellular changes in the arterial vascular bed. The concept of “early vascular aging” and “healthy vascular aging” is defined depending on the ratio of the biological and chronological age of the vessels. The role of diabetes mellitus in increasing vascular stiffness, early vascular aging, as well as the  progression of  atherosclerotic cardiovascular diseases and their complications is considered in detail. Approaches to multifactorial management of vascular age in patients with type 2 diabetes (lifestyle modification with strategy of aggressive treatment of modifiers of atherosclerosis, rejection of bad habits, adherence to dietary recommendations and the use of modern organo- and vasoprotective antidiabetic drugs) are revealed. The mechanism of realization of vasoprotective effects of inhibitors of sodium-glucose transporter-2 (iNGLT-2) is described in detail. The results of completed large random ized trials EMPA-REG Outcome and EMPA-REG BP of the most studied representative of the IGLT-2 group, empagliflozin, are presented. It has been shown that due to their glucose and natriuretic effects, the ability to reduce body weight and blood pressure, improve myocardial metabolism and bioenergetics, decrease the activity of the sympathetic nervous system, as well as positive effects on vascular stiffness, NGLT-2 inhibitors are the drugs of choice in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. This makes it possible to widely use this group of drugs for managing the vascular age of patients and represents a new opportunity in the prevention of vascular aging in T2DM.

This review article discusses the pathophysiological mechanisms of the development of coronavirus infection in obese patients. It has been shown that obesity is considered as the most important risk factor for the development of many comorbid diseases, including severe forms and deaths as a result of a new coronavirus infection. The higher incidence and severity of a new coronavirus infection in obese patients is based on a complex of factors, the main of which are an increase in cardiovascular risk, including a tendency to thrombosis, a decrease in the efficiency of the respiratory system, impaired immune response, and the presence of chronic inflammatory state. The article discusses non-drug approaches and issues of pharmacological therapy in patients with obesity in the context of a pandemic of a new coronavirus infection. It is shown that the implementation of national quarantine measures has led to an increase in physical inactivity, the level of stress and a change in the eating behavior of the population, closing a vicious circle and contributing to an increase in body weight. For this reason, the efforts of physicians of therapeutic specialties should be directed primarily to increasing resistance to infection among obese patients and combating physical inactivity. The main groups of drugs that can be used to combat lipotoxicity are listed. It was noted that infectious disease doctors and endocrinologists can use those groups of drugs that affect the most vulnerable pathogenetic triggers for the development of obesity and comorbidities: hunger and satiety processes, decreased insulin sensitivity, development of lipotoxicity and chronic inflammation. It has been proven that the range of positive effects of new antihyperglycemic drugs from the groups of type 1 glucagon-like peptide agonists and type 2 sodium-glucose transporter inhibitors, combined with a well-studied efficacy and safety profile, represents a new opportunity for the treatment of obesity in the context of a coronavirus infection pandemic.

Введение. Актуальность работы обусловлена необходимостью поиска эффективных и безопасных методов коррекции нарушений адаптации, развивающихся у людей, выполняющих работы в условиях холодного арктического климата с сопутствующими стрессорными факторами. С этой целью разработана экспериментальная модель для исследования влияния комплекса факторов арктического региона на процессы адаптации, а также обоснования методов их фармакологической коррекции. Материалы и методы. Холодо -стрессорная модель представляла собой длительное воздействие на крыс (160 беспородных самцов) низкой положительной температуры воздуха 5 °С при относительной влажности 75-80 % в условиях климатической камеры Feutron (Германия). Дополнительный стрессорный фактор создавали, используя специфический световой режим (круглосуточный свет), звуковую невротизацию (непрерывная громкая рок -музыка), а также ограниченный рацион питания (15 ккал/сут). Изучали динамику ректальной температуры, показателей физической работоспособности в тесте с плаванием, поведенческих реакций в тесте «Открытое поле», количества лейкоцитов, нейтрофилов и лимфоцитов, сывороточных уровней кортизола и инсулина, белков теплового шока HSP-70 и гипоксия -индуцибельного фактора HIF-1α. Результаты. Показано, что на 14-е сутки в условиях моделирования холодо -стрессовых факторов у крыс развивается состояние дезадаптации, характеризующееся развитием гипотермии (до 33 °С), торможением поведенческих реакций, снижением физической работоспособности, признаками иммунодефицита, истощением кортизолового ответа. Для коррекции данных нарушений крысам вводили: плацебо, метапрот в дозах 1, 10, 25, 50, 100 мкг/кг, фенотропил в дозах 50, 100 и 200 мг/кг, кофеин -бензоат натрия в дозах 1, 10, 25, 50 и 100 мг/кг, метапрот 10 мг/кг + фенотропил 100 мг/кг, а также метапрот 50 мг/кг + фенотропил 100 мг/кг. Предложенная холодо -стрессорная модель может использоваться для разработки методов фармакологической коррекции нарушений, развивающихся под действием факторов холодной климатической зоны. Наиболее эффективное действие, позволившее купировать у крыс развившиеся нарушения адаптации, оказали комплексы метапрот 10 мг/кг + фенотропил 100 мг/кг и метапрот 50 мг/кг + фенотропил 100 мг/кг. Background. The search for effective and safe methods for correcting adaptation disorders that develop in people working in a cold Arctic climate with associated stress factors seems to be actual. For this purpose, an experimental model has been developed to study the influence of a complex of factors of the Arctic region on adaptation processes, as well as to substantiate methods for their pharmacological correction. Materials and methods. The cold -stress model represents a long -term exposure of rats (160 outbred males) to a low positive air temperature of 5 °C and relative humidity of 75-80 % in the climatic chamber (Feutron, Germany). An additional stress factor was created using a specific light regimen (24-hour light), sound neuroticism (continuous loud rock music), and a limited diet (15 kcal/day). We studied the dynamics of rectal temperature, physical performance indicators in the swimming test, behavioral reactions in the Open Field test, the number of leukocytes, neutrophils and lymphocytes, serum levels of cortisol and insulin, heat shock proteins HSP-70 and hypoxia -inducible factor HIF-1α. Results. It was shown that on the 14th day of modeling cold -stress factors, rats develop a state of disadaptation, characterized by the development of hypothermia (up to 33 °C), inhibition of behavioral reactions, decreased physical performance, signs of immunodeficiency, depletion of the cortisol response. To correct these disorders, rats were administered: placebo, Metaprot at doses of 1, 10, 25, 50, 100 μg/kg, Phenotropil at doses of 50, 100 and 200 mg/kg, Caffeine -sodium benzoate at doses of 1, 10, 25, 50 and 100 mg/kg, Metaprot 10 mg/kg + Phenotropil 100 mg/kg, and Metaprot 50 mg/kg + Phenotropil 100 mg/kg. Conclusion: The proposed cold -stress model can be used to investigate methods for the pharmacological correction of disorders that develop under the influence of cold climatic zone factors. Metaprot 10 mg/kg + Phenotropil 100 mg/kg and Metaprot 50 mg/kg + Phenotropil 100 mg/kg demonstrated the most effective action in rats, which could make these preparations possible to treat climate -and stress -associated adaptation disorders in human.