[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.

Chronic Critical Illness: Current Aspects of the Problem (Review).

Chronic resuscitation patients who have survived the acute phase of a disease represent a fast-growing cohort of patients requiring specialized medical assistant in intensive care and resuscitation units (ICRU) for several months or years. The term "chronic critical illness" (CCI) was proposed for such patients in the mid-80s of the last century. Patients with CCI make up from 5 to 20% of ICRU. Over time, they develop homeostasis disorders resulting in multiple organ failure and death. Mortality in CCI exceeds that of the majority of malignant neoplasms and functional dependence remains in most of survivors. In the present review, the attempt is made to show the main links of CCI pathogenesis which, if acted upon, can prevent unfavorable outcome. The publications describing epidemiology of CCI, its outcomes, and clinical phenotype have been analyzed. Several researchers consider CCI as a result of persistent inflammation, immunosuppression, and catabolism syndrome. Some works show the importance of nutrition for ICRU patients. The role of gastrointestinal tract in CCI formation has been noted. The effect of intensive therapy on microbiota of the ICRU patients has been demonstrated. Microbiome disturbances in dysbiosis and sepsis have been considered, as well as the effect of intestinal microbiome on the distant organs. Post-intensive care syndrome is a significant constituent of CCI. The main sequelae of the syndrome, as well as the general questions of its prevention and treatment, have been denoted.

Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical Illness (Review).

Dysfunction of the autonomic nervous system (ANS) of the brain in sepsis can cause severe systemic inflammation and even death. Numerous data confirmed the role of ANS dysfunction in the occurrence, course, and outcome of systemic sepsis. The parasympathetic part of the ANS modifies the inflammation through cholinergic receptors of internal organs, macrophages, and lymphocytes (the cholinergic anti-inflammatory pathway). The sympathetic part of ANS controls the activity of macrophages and lymphocytes by influencing ß2-adrenergic receptors, causing the activation of intracellular genes encoding the synthesis of cytokines (anti-inflammatory beta2-adrenergic receptor interleukin-10 pathway, ß2AR-IL-10). The interaction of ANS with infectious agents and the immune system ensures the maintenance of homeostasis or the appearance of a critical generalized infection. During inflammation, the ANS participates in the inflammatory response by releasing sympathetic or parasympathetic neurotransmitters and neuropeptides. It is extremely important to determine the functional state of the ANS in critical conditions, since both cholinergic and sympathomimetic agents can act as either anti- or pro-inflammatory stimuli.

[Invasion-free respiratory monitoring in thoracal surgery of oncology patients]. / Neinvazivnyi respiratornyi monitoring pri torakal'nykh operatsiiakh u onkologicheskikh bol'nykh.

The results of intraoperative monitoring in thoracal surgery of 375 oncology patients with lung cancer were analyzed. The dynamic parameters of ventilation and blood gas composition were investigated in patients with uncomplicated anesthetic management and with complicated adequate ventilation. The diagnostic value of the above parameters is defined for optimizing the respiratory support in surgery for lung cancer.

[Use of pyelo-cystic anastomosis in ureteral obliteration after kidney transplantation]. / Primenenie pielotsistoanastomoza pri obliteratsii mochetochnika posle transplantatsii pochki.

Reconstruction of the urinary tract because of ureteral stricture after kidney transplantation is a serious problem. In development of obliteration of the recipient's ureter near anastomosis and in the absence of own ureters reconstruction is made by pyelocystoanastomosis. A case is reported of a successful use of this method in reconstruction of the urinary tract. Preoperative preparation includes transcutaneous nephrostomy. Sometimes Boary flap is used. The arising reflux had insignificant effect on the transplant's function.

[Changes in mechanical properties of the lungs in thoracic surgery in cancer patients]. / Izmenenie mekhanicheskikh svoistv legkikh pri torakal'nykh operatsiiakh u onkologicheskikh bol'nykh.

Mechanical characteristics of the lungs and time course of their changes at various stages of thoracal surgery were studied in 119 cancer patients. Lung compliance significantly decreased during transfer of the patients into lateral position. The ranges of normal values of lung compliance and aerodynamic resistance at the stage of one-lung ventilation were determined. The studies confirmed the necessity of intraoperative spirometry in the complex of thoracal operation monitoring.

[Optimization of oxygen transport with perfluorane emulsion during surgery of lung cancer]. / Optimizatsiia transporta kisloroda s pomoshch'iu émul'sii perftorana vo vremia operatsii po povodu raka legkogo.

Perfluorane emulsion was included in infusion/transfusion therapy for optimization of oxygen transport. Central hemodynamics was analyzed during the intervention and immediate postoperative period in 80 patients operated on for lung cancer (pneumonectomy, lobectomy, bilobectomy) under conditions of one-lung ventilation. In the control group perfluorane (6 ml/kg) was infused during induction anesthesia. Increased oxygen delivery without increase of cardiac index was observed in the patients treated with perfluorane. Perfluorane had a positive impact on total peripheral resistance during and immediately after the intervention and virtually did not affect other central hemodynamic parameters. Addition of perfluorane to intraoperative infusion therapy improved oxygen budget of operated cancer patients with concomitant therapeutic diseases.

[Antibiotic prophylaxis of postoperative complications in surgical treatment of pulmonary, tracheal and mediastinal tumors]. / Antibiotikoprofilaktika posleoperatsionnykh oslozhnenii pri khirurgicheskom lechenii opukholei legkikh, trakhei i sredosteniia.

A protocol of antibiotic protection, developed and used at Russian Research Center of Roentgenoradiology, is presented. This protocol of perioperative treatment is intended for control of a spectrum of bacterial infections retrospectively detected in patients with lung, tracheal, and mediastinal cancer. The efficiency of perioperative antibiotic prevention is demonstrated as exemplified by 105 patients of different age with various concomitant diseases.