Thermal Balance of the Brain and Markers of Inflammatory Response in Patients with Schizophrenia.

In patients with schizophrenia, the thermal balance of the cerebral cortex was studied by means of microwave radiothermometry method and compared with the markers of systemic inflammation and clinical features of the disease course during therapy. Low temperature heterogeneity of the cerebral cortex was associated with an increase in the activity of inflammatory markers in the blood and, in most cases, with a positive response to therapy. High temperature heterogeneity of the cerebral cortex was typical of patients with insufficient activity of the inflammatory proteolytic system, high levels of antibodies to brain antigens, a more severe course of the disease and, in most cases, with resistance to therapy. A conclusion was made about the diagnostic value of the study of the thermal balance of the brain in patients with schizophrenia.

A Method of Microwave Radiothermometry in Studies of Circadian Rhythms of Brain Temperature.

We studied the possibility of using microwave radiothermometry of the brain in biorhythmology. It was found that the temperature variability of the frontal lobes of the right and left hemispheres strictly corresponded to the 24-h cycle was characterized by the oscillation amplitude of 1.2-1.4°C, which significantly exceeded the amplitude of the basal temperature. A conclusion was made about the informative value of the method of noninvasive registration of the 24-h dynamics of the brain temperature.

[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.

[Metabolic disorders of chronically critically ill patients caused by consequences of traumatic brain injury].

The problem of chronic critical illness therapy is relevant all over the world. Revealing the metabolic function in patients in chronic critical condition is an important link in the development of adequate treatment and rehabilitation tactics. The aim - identification of metabolic features in chronic critical patients after brain injury in the first 3 days from the moment of admission to the rehabilitation center. Material and methods. Single-center observational study included a group of 25 patients with chronic critical illness, aged 38.7±14.0 years with body mass index 20.8± 4.3 kg/m2 (min 14.5; max 29.7), who were on independent breathing through a tracheostomy tube, and who have pronounced neurological disorders in the form of depression of minimally conscious state, FOUR scale from 12 to 16 points, as well as bedsores 1-2 stage and polysegmental pneumonia. The patients underwent indirect calorimetry and analysis of biochemical parameters of protein, carbohydrate, fat and mineral metabolism, as well as the level of nitrogen excretion with urine. Results and discussion. The data obtained indicate that chronic critical ill patients with the consequences of traumatic brain injury had pronounced metabolic disorders, mainly of a protein component. Total protein level decreased up to 61.0±9.4 g/l (min 39.1; max 83.1), albumin up to 30.2±6.0 g/l (min 17.4; max 37.8), prealbumin up to 0.13± 0.06 g/l (min 0.04; max 0.23) and transferrin up to 147.7±37.7 mg/dl (min 84.0; max 209.0). The patients' requirement in protein was 106.4±38.5 g/day (min 57.1; max 160.5) or 1.55±0.46 g/kg/day (min 0.75; max 2.22). The level of resting energy expenditure measured by indirect calorimetry was 1549.1±421.8 kcal/day (min 673.0; max 2430.0) or in terms of body weight 24.8±7.6 kcal/kg/day (min 12.4; max 45.8). Conclusion. The data obtained indicate a continuing catabolic phase in patients more than 30 days after the primary injury, which led to their chronic critical condition.

[Intestine morphology and microbiocenosis changes in critically ill patients in neurosurgery]. / Izmenenie morfologii i mikrobiotsenoza kishechnika u neirokhirurgicheskikh patsientov v kriticheskom sostoyanii.

In recent years, the effect of critical conditions on intestine and the role of such changes in maintenance and progression of systemic disorders are of particular attention. This issue is relevant in critically ill neurosurgical patients too. Intestine morphology and microbiome changes in these patients represent a wide field for researches in intensive care and prevention of secondary damage to other organs and systems. This review ensures a current approach to the problem of intestine morphology and microbiome changes in critically ill neurosurgical patients. We reviewed the data from clinical studies and experiments reproducing a critical condition in animals. Most publications are indexed in the PubMed, e-library, Google Scholar databases. We also analyzed the data from NEJM, JAMA, Lancet, Critical Care and other issues. The manuscript contains an overview of 44 foreign and 13 domestic references; over 50% of researches were published within the past 5 years. Searching depth was over 50 years.

[Vegetative State: Difficulty in Identifying Consciousness and Predicting Outcome].

Article consists of literature review, authors experience of the application of neurovisualization and neurophysiological research methods to predict the recovery of consciousness in patients in vegetative state (VS). According to the literature data PET with FDG has higher sensitivity in the detection of signs of consciousness, then functional MRI (fMRI). The method fMRI allows assessing the functional activity of the brain in a state of rest and in response to stimulation with different modalities ­ visual, auditory, etc (with the application of active and passive paradigm). A higher specificity in the detection of signs of consciousness have the methodology of fMRI with the active paradigm, at the same time, the absence of signs of consciousness according to the fMRI can not be charged as a basis for the conclusion of a poor prognosis in a particular patient. Neurophysiological tests (EEG, TMS, EP, etc) are more readily available and quite effective. Based on the literature analysis, the authors comes to the conclusion that neurovisualization and neurophysiological tests used in the prediction of the outcome of VS reflects the residual functional activity of different brain areas, in a context of diffuse brain damage, and the recovery of consciousness is usually combined with the restoring of the functional activity off the thalamocortical tracts, which activity, indirectly, is evaluated using these methods. In the authors' opinions, the main disadvantage in the interpretation of the is the lack of a common pathophysiological concept of the organization of brain functions in VS patients. The authors offer for the discussion their concept of stable pathological states of the brain, which is based on the works of Russian pathophysiologists.

[Craniocerebral hypothermia in the acute period of ischemic stroke]. / Kraniotserebral'naya gipotermiya v ostreishem periode ishemicheskogo insul'ta.

OBJECTIVE: To determine the effect of craniocerebral hypothermia (CCH) on neurological deficit regression, hemodynamics, fever and functional outcome of therapy in patients with moderate ischemic stroke (IS). MATERIAL AND METHODS: This study included 60 patients with IS (the first day). The main group consisted of 30 patients who underwent CCH, and the comparison (control) group consisted of 30 patients without CCH. The National Institutes of Health Stroke Scale (NIHSS), the Glasgow Coma Scale (GCS), the modified Rankin Scale (mRs) were used. Recorded parameters were mortality, heart rate (HR), blood pressure (BP), axial temperature, cerebral temperature of the frontal cortex. Cerebral temperature was obtained noninvasively by using a RTM-01-RES radiothermometer (Russia). CCH (for 24 hours) in the main group was implemented by ATG-01 device (Russia). Results were recorded on the day of admission, after 24 hours and at discharge. In both groups, basic neuroprotective, hypotensive, antiplatelet and antiedemic therapy was administered. RESULTS: No fatal outcomes were reported in both groups. Side-effects and complications of CCH were not recorded. In the main group, neurological deficit assessed by NIHSS decreased by 75% after the CCH procedure and by 93.75% at the time of discharge from the hospital. In patients of the comparison group, regression of neurological deficit was 35% on the second day and 55% at the day of discharge. The use of CCH suppressed systemic and cerebral hyperthermia. Functional outcome of therapy in the main group was higher compared to the comparison one. The dynamics in blood pressure and heart rate didn't differ in both groups. CONCLUSION: A pronounced positive effect of CCH on the course of the acute period and therapy results in patients with IS was demonstrated.

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.

[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.

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.

Prediction of the Effectiveness of Spontaneous Breathing in Patients with Brain Damage of Various Etiologies.

The aim of the study was to develop an informative method for assessing chemoreflex sensitivity and to evaluate its prognostic capacity for restoring spontaneous breathing in patients with brain damage of various etiologies. The study included 16 healthy volunteers and 38 patients on prolonged mechanical ventilation (VE) after a traumatic brain injury, anoxic brain damage, and cerebrovascular events. The external respiration variables were assessed from the initial level to the development of the first episode of desaturation with spO2 in the range of 90-80% against the background of normobaric hypoxia as indicators reflecting the development of adaptive ventilatory response and characterizing the state of peripheral chemoreflex sensitivity (PCS). The peripheral chemoreflex sensitivity index (PCSI) was calculated using the equation: PCSI = [RR(e) : RR(i)] × [Vt(e) : Vt(i)] × [VE(e) : VE(i)] × Vt(e) × VE(e), where PCSI is the peripheral chemoreflex sensitivity index in L2/min; RR(i) and RR(e); Vt(i) and Vt(e); VE(i) and VE(e) are the respiratory rate, tidal volume, minute ventilation initially (i), before a functional stress test, and during a functional test of normobaric hypoxia with spO2 in the range of 90-80% (e). With the PCSI values ≥15.6 L2/min, successful weaning from ventilators and recovery of spontaneous breathing are predicted. The sensitivity and specificity of PCSI were 78.57 [95% CI: 49.2-95.26] and 83.3% [95% CI: 62.6-95.26], respectively. The sensitivity and specificity of the traditional indicator of the success rate of weaning from ventilators and recovery of spontaneous breathing, Rapid Shallow Breathing Index (RSBI), in this cohort of patients was 69.23 [95% CI: 38.6-90.9] and 28.0% [95% CI: 12.03-49.3], respectively. A predictor of the patient's weaning from mechanical ventilation is the assessment of peripheral chemoreflex sensitivity, which can be measured by a simple non-invasive bedside test based on measuring the difference in external ventilation parameters before and during a functional normobaric hypoxic trial.

Binding of pyridoxal, pyridoxal 5'-phosphate and derived hydrazones to bovine serum albumin in aqueous solution.

In the present paper, the kinetics of a reaction between bovine serum albumin (BSA) and pyridoxal, pyridoxal 5'-phosphate was studied, apparent rate constant of product formation and dissociation as well as binding constants were determined. Pyridoxal 5'-phosphate hydrazones of isonicotinic, picolinic, 2-furoic, thiophene-2-carboxylic, pyrazinoic acids binding to BSA was studied by spectrofluorimetry, stability constants of the associates were calculated from experimental data using maximal likelihood approach. The changes in the secondary structure of BSA induced by hydrazones addition were studied by IR spectroscopy. New freely available software for curve fitting was developed as a part of the software kit designed for the solution chemistry and used for a specific problem of this study, IR spectra processing.

Reversible charge separation followed by exciplex formation.

The quenching of fluorescence by reversible bimolecular ionization, followed by reversible exciplex formation from an ion pair (Scheme II) subjected to spin-conversion and subsequent radical-ion recombination/separation, has been studied by means of integral encounter theory (IET) and fitted to the available experimental data. Using the incoherent (rate) model of spin-conversion, the ion recombination to the excited triplet products is also accounted for. All of the results are obtained and shown to be different for the pulse excitation of fluorescence and its stationary detection. The free-energy dependence of all of the calculated properties of the forward and backward electron transfer are specified and compared with the conventional free-energy gap (FEG) law.

Reversible exciplex formation followed charge separation.

The reversible exciplex formation followed by its decomposition into an ion pair is considered, taking into account the subsequent geminate and bulk ion recombination to the triplet and singlet products (in excited and ground states). The integral kinetic equations are derived for all state populations, assuming that the spin conversion is performed by the simplest incoherent (rate) mechanism. When the forward and backward electron transfer is in contact as well as all dissociation/association reactions of heavy particles, the kernels of integral equations are specified and expressed through numerous reaction constants and characteristics of encounter diffusion. The solutions of these equations are used to specify the quantum yields of the excited state and exciplex fluorescence induced by pulse or stationary pumping. In the former case, the yields of the free ions and triplet products are also found, while in the latter case their stationary concentrations are obtained.

Slipped loop structure of DNA: a specific nucleotide sequence forms only one unique conformer.

Earlier with some DNA sequences we were able to prove the existence of a new polynucleotide chain folding named slipped loop structure, or SLS [1,2]. However, the possibility of the presence of two SLS isomers in equilibrium was not excluded in the experiments. Here we are dealing with a specially designed structure formed by two short oligonucleotides intended for avoiding such a situation. To minimize the possibility of alternative structure formation and stabilize the conformation under investigation, the oligonucleotide sequences were designed in such a way that the bimolecular structure SLS31 would have two binding sites for antibiotic distamycin A. The sample was exposed to chemical probing both in the presence of distamycin A and without the ligand and the accessible nucleotides were mapped. The results do not suggest the presence in the solution of two isomers with different types of loop slippage without interloop interactions and strongly support the formation of a unique slipped loop conformation stabilized by an additional interloop helix, or slipped loop structure.

Experimental evidence for slipped loop DNA, a novel folding type for polynucleotide chain.

DNA regions with short direct repeats (5-7bp) with a spacer in between, when under super-helical stress, are known to become susceptible to single-strand specific nuclease S1. This is in accord with formation of two shifted loops protruding from the opposite chains. Such type of folding could have been additionally stabilized by base pairing between the complementary parts of the loops that explains existence of the protected from S1 moieties of the loops. To test this possibility we designed and synthesized an oligonucleotide of 56 bases, so that it forms a hairpin with a stem which fails to acquire a traditional helix due to a special sequence but may favor the formation of the proposed Slipped Loop Structure (SLS). The oligonucleotide folding was studied by a chemical modification method at one nucleotide level resolution. Three zones, protected from the used probes were found: the one that forms the stem, and the others that are located within the two by-loops in those moieties which have the base pairing potential. Proceeding from the data obtained and stereochemical analysis a 3-D scheme for the SLS form of DNA is suggested.

[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.

[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.

[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.

[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.