[Staged treatment of a patient with malignant ischemic cerebral infarction]. / Sluchai etapnogo lecheniya patsienta so zlokachestvennym ishemicheskim infarktom mozga.

The authors discuss surgical decompression of the brain in patients with malignant ischemic cerebral infarcts. Successful staged treatment of a middle-aged patient with malignant ischemic stroke in the middle cerebral artery basin is presented.

CLINICAL AND FUNCTIONAL STATE OF THE THYROID GLAND IN WOMEN OF PERI- AND POSTMENOPAUSAL AGE WITH METABOLIC SYNDROME.

The article deals with the problem of the clinical and functional relationship between the state of the thyroid gland in women of menopausal age and the components of the metabolic syndrome (MS). The purpose of the study: to assess the relationship between thyroid dysfunction and various components of MS in women of peri- and postmenopausal age. 80 menopausal women (mean age 55 years) were examined, of which 40 people with MS constituted the main group, and the comparison group - a similar number of women without MS. The inclusion criterion in the study was the presence of signs of abdominal obesity (AO) according to the WHO criteria (2008). Anthropometric, functional (BP), laboratory (lipidogram, TSH, freeT4, antibodies to TPO, FSH, LH, urinary iodine concentration) and instrumental (ultrasound of the thyroid gland) data, statistical analysis using the program SPSSStatistics version 20 were evaluated. The women were divided into two age groups: group 1 - perimenopausal and group 2 - postmenopausal. There were 40 people in each group (20 women with MS and 20 women without MS). It has been shown that peri- and postmenopausal women with MS have subclinical hypothyroidism. The influence of peripheral blood TSH levels in peri- and postmenopausal women with MS on body weight, carbohydrate and lipid metabolism, and sex hormones was established.

[INDICATORS OF CARDIOHEMODYNAMICS OF RHYTHM DISTURBANCES IN ELDERLY PEOPLE WITH CHRONIC HEART FAILURE].

The aim of our study was to study and analyze the electrophysiological indicators of rhythm disturbances in heart failure in elderly people who participated in the elimination of the consequences of the Chernobyl accident in the distant period. In order to assess the functional features, 50 elderly patients (65-74 years old) who participated in the liquidation of the consequences of the Chernobyl accident were examined. Patients were divided into 4 groups depending on the length of stay in an environmentally disadvantaged zone: group 1 (April-June 1986) - 8 (16%) people; 2 (June-December 1986) -14 (28%); 3 (1987-1989) -17 (34%) and group 4 (1990-91gg) -11 (22%) people. All patients were on basic therapy. To study cardiogemodynamics in this category of patients, the following electrophysiological research methods were performed: ECG, XM ECG, SMAD, EchoCG. When analyzing electrophysiological studies, the MSExcel and Statistica programs were used. The examined patients showed a high incidence of left ventricular hypertrophy and cardiac arrhythmias. So in the 1st and 2nd groups, atrial fibrillation, sinus tachy and bradycardia, AV blockade of 1-2 degrees were reliably detected. In groups 3 and 4, left ventricular hypertrophy and arrhythmias were detected with a lower frequency. It should be noted that these changes were observed in individuals participating in the LPA from April to December 1986, i.e. in the first year after the accident. According to echocardiography, diastolic dysfunction of the left ventricle was found mainly in individuals of 1-2 groups. High high indices of KDR, BWW and KSO in 1-2 groups are noted. LVMI exceeds its norm in all studied groups. Thus, statistically significant differences of some indicators are revealed with electrophysiological research methods in all groups of elderly patients with heart failure participating in the liquidation of the Chernobyl accident, as well as the high incidence of rhythm disturbances in patients with Chernobyl nuclear power plants.

The Effect of Nitroxyalkyl Succinimides on Activity of Cyclic Guanosine Monophosphate Phosphodiesterase.

The effect of N-nitroxymethyl succinimide (1), N-(2-nitroxyethyl) succinimide (2) and N-(3-nitroxypropyl) succinimide (3) on enzymatic activity of cyclic guanosine monophosphate (cGMP) phosphodiesterase was studied and crystal structure of compound (2) was determined. It was shown that all studied N-nitroxy succinimides inhibited cGMP phosphodiesterase in a concentration range of 0.1-0.001 mM. Compound (2) noncompetitively and reversibly inhibited hydrolytic function of enzyme with Ki=1.7×10-5 М. Inhibition constant for the reference compound N-(2-nitroethyl) nicotinamide (nicorandil) was 3×10-5 М.

[ARTERIAL HYPERTENSION AMONG WORKERS OF A URANIUM PROCESSING ENTERPRISE OF THE REPUBLIC OF KAZAKHSTAN: PREVALENCE, RELATIVE RISKS AND PREDICTORS OF THE DEVELOPMENT].

The aim of this study was to establish the prevalence, relative risks, and predictive factors of the development of arterial hypertension (AH) in workers of a uranium processing enterprise (UPE). An open cross-sectional comparative study of 809 UPE workers was conducted. The compared them to the 696 workers of the bearing plant, located at a distance of 10 km from UPE. Stratification was performed and odds ratios (OR), gross (RR) and standardized relative (SRR) risks of hypertension were calculated. Our results revealed a high prevalence of hypertension among UPE workers (24.8%), as well as greater risk of development of hypertension among workers of UPE in comparison to the personnel of the non-uranium enterprise: RR=2.4 and SRR=2.9. The most significant predictors of hypertension were burdened heredity (OR = 13.6), total radiation dose (OR=1.5), overweight (OR=1.1), high anxiety (OR=0.5) and systematic use of alcohol (OR=0.5). Thus, among workers chronically exposed to radiation toxicity, high prevalence of hypertension, excessive RR and SRR of developing hypertension and the presence of risk factors for hypertension were established.

The Knife's Edge of Tolerance: Inducing Stable Multilineage Mixed Chimerism but With a Significant Risk of CMV Reactivation and Disease in Rhesus Macaques.

Although stable mixed-hematopoietic chimerism induces robust immune tolerance to solid organ allografts in mice, the translation of this strategy to large animal models and to patients has been challenging. We have previously shown that in MHC-matched nonhuman primates (NHPs), a busulfan plus combined belatacept and anti-CD154-based regimen could induce long-lived myeloid chimerism, but without T cell chimerism. In that setting, donor chimerism was eventually rejected, and tolerance to skin allografts was not achieved. Here, we describe an adaptation of this strategy, with the addition of low-dose total body irradiation to our conditioning regimen. This strategy has successfully induced multilineage hematopoietic chimerism in MHC-matched transplants that was stable for as long as 24 months posttransplant, the entire length of analysis. High-level T cell chimerism was achieved and associated with significant donor-specific prolongation of skin graft acceptance. However, we also observed significant infectious toxicities, prominently including cytomegalovirus (CMV) reactivation and end-organ disease in the setting of functional defects in anti-CMV T cell immunity. These results underscore the significant benefits that multilineage chimerism-induction approaches may represent to transplant patients as well as the inherent risks, and they emphasize the precision with which a clinically successful regimen will need to be formulated and then validated in NHP models.

[The use of transcallosal ventriculostomy to treat complicated forms of aneurismal intracranial hemorrhages].

The present paper reports two cases of successful use of the anterior interhemispheric transcallosal approach during ultra-early surgery in patients in decompensated condition with severe intraventricular hemorrhage caused by rupture of cerebral aneurysms.

Effect of highly mineralized natural water on redox processes in HaCaT keratinocytes.

We studied ROS production by HaCaT keratinocytes, the state of transmembrane mitochondrial potential, and activation of transcription factor Nrf2 in response to brine exposure. It was demonstrated that this exposure induces rapid but moderate decrease in mitochondrial potential, stimulates ROS production, and leads to activation of transcription factor Nrf2.

Protective effect of ARE-inducing phenol antioxidant TS-13 in chronic inflammation.

The protective effect of partially substituted monophenol TS-13 inducing the Nrf2/Keap1/ARE signaling system was studied on the model of chronic inflammation in vivo. It was found that during simulation of inflammation in an air pouch lined with synovial-like membrane, TS-13 did not affect the exudate volume, protein content, and cell count, but significantly reduced the intensity of oxidative metabolism in leukocytes of the exudate. In rheumatoid polyarthritis induced by heterologous collagen, TS-13 reduced the severity of clinical signs of inflammation only at the early stages, but inhibited H2O2 generation by monocytes and, partially, by blood neutrophils. These results suggest that the phlogolytic effect of the redox sensitive Nrf2/Keap1/ARE signaling system is less pronounced in chronic immune-mediated inflammatory processes than in acute inflammation.

Anti-inflammatory activity of TS-13, ARE-inducing phenol antioxidant.

The protective effect of water-soluble TS-13 monophenol inducing the antioxidant-responsive element (ARE) system was studied on the models of acute inflammation. Intragastric administration of TS-13 to rats significantly reduced the severity of acute aseptic inflammation induced by intravenous injection of zymosan particles: granulocyte blood count and volume density of infiltrates in the liver decreased on day 3, spontaneous production of activated oxygen metabolites and respiratory burst in blood granulocytes decreased on days 2 and 3. A single dose of TS-13 improved survival of mice with endotoxin shock induced by intraperitoneal injection of E. coli LPS. These results confirmed high anti-inflammatory activity of TS-13.

[Oxidised dextrans influence on reactive oxygen species generation by murine peritoneal exudate phagocytic cells].

The effects of oxidized dextrans of different molecular weight on reactive oxygen species production and transmembrane mitochondrial potential of macrophages and neutrophils have been studied in vivo and in vitro. Oxidised dextrans demonstrated moderate direct antioxidant ability but induced intracellular oxidative stress through the increase of oxygen radical generation. This effect of the investigated compounds amplifies the cytotoxic and bactericidal potential of phagocytes and can influence isoniazid metabolism, thus increasing its efficiency in therapy of infectious diseases.

Keap1/Nrf2/ARE redox-sensitive signaling system as a pharmacological target.

The redox-sensitive signaling system Keap1/Nrf2/ARE plays a key role in maintenance of cellular homeostasis under stress, inflammatory, carcinogenic, and proapoptotic conditions, which allows us to consider it as a pharmacological target. Here we review the basic regulatory mechanisms of the Keap1/Nrf2/ARE system, key targets for pharmacological intervention, and interconnection of this system with other redox-sensitive transcriptional factors. We also discuss the range of currently available pharmaceuticals. Finally, we promote "indirect" antioxidants as a promising strategy for prevention and treatment of wide range of diseases associated with oxidative stress.

[Combination of multiple distal posterior fossa aneurysms with cerebellar AVM].

A rare combination of distal aneurysms of SCA and PICA with cerebellar AVM is presented. Case report demonstrates successful simultaneous surgical treatment of all abovementioned anomalies.

[Stepwise treatment of a patient with seven bilateral cerebral aneurysms].

This case report describes successful multistage combined treatment of a female patent with seven bilateral cerebral aneurysms.

Changes in activity of free radical oxidation processes in the early stages of BCG granulomatosis.

We studied the intensity of free radical oxidation in the liver and activity of oxidative metabolism in mouse peritoneal exudate phagocytes at the early stages of chronic generalized BCG-induced granulomatosis (days 3 and 30 after a single intraperitoneal or intravenous administration of 0.5 mg of BCG vaccine). It was found that both methods of injection did not change the intensity of free radical lipid peroxidation in the liver in comparison with the control, but activity of free radical oxidation mediated by production of hydrogen peroxide was increased in the liver and peritoneal exudate at the stages of mature granuloma formation (day 30). At the same time, intraperitoneal injection contributed to more pronounced activation of lipid peroxidation and synthesis of hydrogen peroxide in the liver.

ARE-inducing phenol antioxidant TC-13 improves survival of Drosophila melanogaster in oxidative stress.

The effects of hydrophilic synthetic antioxidant TC-13 sodium (3'-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate on survival of various strains of Drosophila melanogaster were studied under conditions of oxidative stress induced with H(2)O(2)and paraquat. In a concentration of 1%, TC-13 significantly improved survival of Canton S males treated with H(2)O(2)and in a concentration of 0.2% it improved survival of H(2)O(2)-stressed Oregon R females. The protective effect of the antioxidant under conditions of paraquat-induced stress was observed in Canton S females and Oregon R flies of both genders. Addition of T-13 to diets led to prolongation of the maximum lifespan of insects in the majority of the experiment variants. A relationship between the protective effects of TC-13 and the genotype, gender, and environmental conditions was detected.

Mechanism of the Nrf2/Keap1/ARE signaling system.

Nrf2 regulates expression of genes containing antioxidant-respons(iv)e element (ARE) in their promoters and plays a pivotal role among all redox-sensitive transcription factors. Nrf2 is constitutively controlled by repressor protein Keap1, which acts as a molecular sensor of disturbances in cellular homeostasis. These molecular patterns are in close interconnection and function as parts of the integrated redox-sensitive signaling system Nrf2/Keap1/ARE. Depending on cellular redox balance, activity of this signaling system changes at the levels of transcription, translation, posttranslational modification, nuclear translocation of transcription factor, and its binding to ARE-driven gene promoters. This review summarizes current conceptions of Nrf2/Keap1/ARE induction and inactivation.

Morphofunctional characteristics of the immune system in CBA and C57Bl/6g mice.

We studied peculiarities of morphofunctional organization of the immune system in C57Bl/6g and CBA mice differing by their susceptibility to various types of infectious agents. The revealed differences in the structure of lymphoid organs, T lymphocyte subpopulation ratio and their differentiation into Th1/Th2 cells after mitogen stimulation drove us to a conclusion on genetically determined regularities in the development of the immune response in these animal strains.

[Redox-dependent signaling system Nrf2/are in inflammation].

Transcription factor Nrf2 plays a key role in cell defense against oxidative stress, as well as in counteracting chemical and physical factors that induce apoptosis and carcinogenesis. The mechanism of Nrf2/ARE redox regulation and ARE-mediated gene expression are analyzed in the review. Special attention was paid to anti-inflammatory effects of Nrf2/ARE system, which significantly manifest in Nrf2 knockout animal.

Synthetic water-soluble phenolic antioxidant regulates l-arginine metabolism in macrophages: a possible role of Nrf2/ARE.

Synthetic water-soluble phenolic antioxidant TS-13 exhibits pronounced anti-inflammatory properties in vivo and induces intracellular signal system Nrf2/ARE. At concentrations 150-1000 microM it inhibits nitric oxide (NO) production in mouse peritoneal macrophages. However, this compound at low concentrations (1-100 microM) paradoxically increases NO production and decreases activity of arginase. These results are indicative of an ambiguous role of NO and its metabolites in the mechanism of development of inflammatory reaction.