Development Of Tissue Hypoxia Research Articles

The study of hemoglobin forms under the conditions of energy drink consumption

In today’s world, where stress and busyness are an integral part of everyday life, energy drinks have become not only a means of satisfying the need for energy and maintenance of vitality, but also a symbol of lifestyle, an important element of the modern culture of consumption. The speed and efficiency they promise attract the attention of consumers, especially those who are constantly on the move. Such drinks have become popular not only among young people, but also among everyone who seek to maintain their activity and efficiency during the day. The purpose of the work was to investigate the dynamics of changes in the level of total hemoglobin and its forms, in particular oxy-, carboxy-, sulf-, met-, and dyshemoglobin under the conditions of energy drink consumption. The study was conducted using male Wistar rats weighing 150–220 g kept in the vivarium under appropriate lighting conditions, temperature, humidity and standard diet. All the animals had free access to feed (based on daily requirements) and water (based on 20 ml of water per rat per day). The experiment was carried out in compliance with the requirements of the European Convention for the Protection of Vertebrate Animals used for Experimental and Scientific Purposes (Strasbourg, 1986). The animals were divided into five groups: the 1st group received drinking water (intact control); the 2nd–5th groups received daily the non-alcoholic energy drink “Burn” per os for a month. The calculation of the required amount of drink for administration per one rat was based per 1 kg of body weight. To monitor the growth and development, we weighted the rats at the beginning and at each stage of the experiment. The material (blood) was taken on the 1st (2nd group), 10th (3rd group), 20th (4th group) and 30th day (5th group) after the completion of the experiment under anesthesia (intramuscularly sodium thiopental, 60 mg/kg). The total hemoglobin level was determined with the Mythic 18 hematological analyzer. Determination of the content of oxyhemoglobin, methemoglobin, sulfhemoglobin and carboxyhemoglobin was performed spectrophotometrically. The obtained data indicate significant changes in both the total level of hemoglobin and its ligand forms, in particular, a decrease in the level of oxyhemoglobin and the accumulation of dyshemoglobins, such as methemoglobin, sulfhemoglobin, and carboxyhemoglobin. As evidenced by the obtained results, the consumption of energy drinks leads to the oxygen homeostasis violation, the development of tissue hypoxia and can cause structural and functional disorders in the body under such conditions.

Correction of metabolic changes in the tissues of oral cavity of rats using a complex of drugs under the conditions of pathological factors

Hypoxia is a typical pathological process that occurs when tissues are insufficiently supplied with oxygen or when its utilization is impaired. One of the most important pathogenetic factors in the development of tissue hypoxia is the disintegration of the structure of mitochondrial membranes which occurs under the influence of various etiological factors. In children who suffered hypoxia in the antenatal period, the frequency of developmental delays is significantly increased, and the incidence of caries is also shown to increase as compared to healthy children. Based on the above, this work is relevant for modern dentistry. The work is devoted to the study of the state of the maxillofacial system and tissues of the oral cavity of rats under the influence of the complex of drugs under the conditions of intrauterine hypoxia, cariogenic diet, thyroid insufficiency and fluorine deficiency. The subjects of the study were 25 female white rats of the Wistar line of herd breeding from the vivarium of the SE “ISMFS NAMS” kept on a standard vivarium diet. The animals were divided into three groups – intact (7 rats), pathology model (8 rats), pathology model and drug complex (8 rats). Animals were removed from the experiment under thiopental anesthesia (40 mg/kg). Lower jaws and pulp were removed. As a result of the research, it was established that the proposed treatment-prophylactic complex has a pronounced caries-prophylactic and periodontoprotective effect. The caries-preventive effectiveness of the complex was due to its ability to stimulate the mineralizing function of the dental pulp, namely, to increase the activity of alkaline phosphatase of the pulp, as an indicator of the activation of osteoblasts, against the background of a decrease in the activity of acid phosphatase, a marker of osteoclasts.

Morphological changes of sexually mature rat's pineal gland and cerebellar cortex under long-term exposure to heavy metal salts

Pollution with heavy metal salts is an important environmental problem today, having an adverse effect on public health. The endocrine system maintains homeostasis in the body. The purpose of the work is to study the morphological changes of the cerebellar cortex and epiphyses of sexually mature male rats under the condition of long-term exposure to the body of a complex of heavy metal salts. The morphological changes in the cerebellar cortex and epiphysis of sexually mature male rats under the condition of long-term exposure to heavy metal salts was studied. Animals of the experimental group were simulated microelementosis by adding to drinking water a mixture of heavy metal salts for 60 days: zinc (ZnSO4×7H2O) – 5 mg/l, copper (CuSO4×5H2O) – 1 mg/l, iron (FeSO4) – 10 mg/l, manganese (MnSO4×5H2O) – 0.1 mg/l, lead (Pb(NO3)2) – 0.1 mg/l and chromium (K2Cr2O7) – 0.1 mg/l. Morphological, morphometric and statistical research methods were used. Long-term (60-days) intake of heavy metal salts mixture in the body of experimental animals leads to the development of the general adaptation syndrome, the stage of chronic stress “subcompensation” in the pineal gland. Morphological changes in the organs had a nonspecific polymorphic character, such as a sharp violation of hemodynamics, a violation of the morphology of the vascular wall, the state of pinealocytes and Purkinje cells, the development of tissue hypoxia, processes of apoptosis and reactive astrogliosis as a response to the action of a damaging agent. The pineal gland of the experimental animals showed signs of indole production, but the evacuation of hormones (including melatonin) into the vascular bed was hampered due to the violation of the morphology of the vascular wall and the cell membrane of pinealocytes. This led to a deficiency of this hormone in the body of the experimental animals, which negatively affected the adaptive processes in the cerebellar cortex in response to the action of the stress agent. Compensatory and adaptive processes in the pineal gland and cerebellar cortex had signs of functional stress. Adaptive processes were observed both in a small number of pinealocytes and in Purkinje cells, as well as an active adaptive glial reaction in both organs.

EFFECT OF ENERGY DRINK ON LIGAND FORMS OF HEMOGLOBIN

The article is devoted to the study of the effect of energy drink on ligand forms of hemoglobin in experimental animals. According to our results, the consumption of energy drink causes significant changes in both the total level of hemoglobin and its ligand forms. In particular, we have established a reduction of oxyhemoglobin and accumulation of dyshemoglobin: methemoglobin, sulfhemoglobin and carboxyhemoglobin, which in turn affects the oxygen homeostasis of the body, the development of tissue hypoxia and can cause structural and functional disorders in the body under such conditions.

A Response of the Pineal Gland in Sexually Mature Rats under Long-term Exposure to Heavy Metal Salts.

Pollution with heavy metal salts is an important environmental problem today, having an adverse effect on public health. The endocrine system maintains homeostasis in the body. The antioxidant protection (GPX-1) of the pineal gland in mature rats was studied. Animals of the experimental group represented a model of microelementosis, achieved by adding a mixture of heavy metal salts for 90 days to drinking water: zinc (ZnSO4×7H2O) - 5 mg/l, copper (CuSO4×5H2O) - 1 mg/l, iron (FeSO4) - 10 mg/l, manganese (MnSO4×5H2O) - 0.1 mg/l, lead (Pb(NO3)2) - 0.1 mg/l, and chromium (K2Cr2O7) - 0.1 mg/l. Morphological, statistical and immunohistochemical (GPX-1) research methods were used. Long-term (90-days) intake of heavy metal salts mixture in the body of experimental animals brought about development of the general adaptation syndrome, the stage of chronic stress "subcompensation" in the pineal gland. Morphological rearrangements were of nonspecific polymorphic nature as severe hemodynamics disorder in the organ, impairment of vascular wall morphology, development of tissue hypoxia and oxidative stress, accompanied by processes of accelerated apoptosis in part of pinealocytes, by a significant decrease in glutathione peroxidase level in the organ and reactive astrogliosis as a response to the damaging agent's action. Along with the negative changes in the pineal gland, a compensatory-adaptive processes with signs of functional stress also occurred. A sufficiently high degree of glutathione peroxidase activity in 39% of pinealocytes located perivascularly, active adaptive glial reaction and activation of synthetic processes in some pinealocytes were also observed.

Hiperbarična oksigenacija kao pretretman i tretman u ishemijsko-reperfuzijskom oštećenju

Tissue ischemia means insufficient blood flow to a certain area of the body. Interruption of the arterial blood supply leads to an imbalance between metabolic supply and demand and the development of tissue hypoxia. Tissue hypoxia induces metabolic changes that result in inflammation, increased production of reactive oxygen species, and cell death. If adequate blood flow is established in the ischemic tissue, there will be an increase in cellular damage, which is referred to as ischemic-reperfusion injury. Ischemia and ischemia-reperfusion injury are at the root of numerous diseases widely present in modern society, such as myocardial infarction, cerebral insult, acute kidney injury. For now, there is no way to directly affect cellular hypoxia, but the clinical treatment of hypoxic conditions is aimed at modulating global hypoxemia and increasing the amount of oxygen dissolved in the blood. Hyperbaric oxygenation (HBO) is a treatment during which the patient breathes 100% oxygen under a pressure of at least 1.4 atmospheres. Although the use of hyperbaric therapy was recorded as early as the 17th century, today this treatment is approved for a few indications.

Оксидантный стресс и тканевая гипоксия как факторы, способствующие развитию дисфункции предстательной железы и мочевого пузыря при метаболическом синдроме

Introduction. The development of oxidative stress and nonspecific inflammation is one of the leading factors in the development of benign prostatic hyperplasia (BPH) and associated urination disorders in metabolic syndrome (MS). However, the specific mechanisms of these processes are not entirely clear. The purpose of the study. To study the activity of reactive oxygen species production and the functional state of mitochondria in the prostate and bladder and their role in the dysfunction of these organs using an experimental model of MS induction in rats. Material and methods. In 10 adult mongrel male rats MS was induced by keeping them on a high-calorie diet with an increased content of carbohydrates and fats for 3 months. 10 rats kept on a standard vivarium diet served as controls. The development of MS was confirmed by characteristic changes in the biochemical analysis of blood (hyperglycemia, hyperuricemia, dyslipidemia, hyperinsulinemia). In both series of rats, sections of the native prostate and bladder were examined by laser confocal microscopy and stained with fluorescent probes that characterize the activity of the production of reactive oxygen species (dichlorofluorescein-DCF) and the functional state of the mitochondria (tetramethylrodamine ether – TMRE). The activity of a number of intracellular enzymes (AST, ALT. Alkaline phosphatase, LDH) was investigated in the tissues and urine. Results. In rats with MS, the development of BPH and hypertrophy of the bladder were revealed, confirmed histologically. The study of sections of both organs by confocal microscopy revealed a significant increase in the production of reactive oxygen species by their cells and a decrease in the functional activity of mitochondria, which indicated the development of oxidant stress and tissue hypoxia. In the prostate, this was accompanied by a decrease in the secretory activity of the prostate glands, and in the bladder – the release of cytoplasmic enzymes from damaged cells into the urine, indicating cell damage. Conclusion. The causes of the development of a non-specific inflammatory process in the prostate and bladder, leading to dysfunction of these organs in MS, are increased production of reactive oxygen species and the development of tissue hypoxia.

DYNAMICS OF HISTAMINE LEVEL IN THE BLOOD PLASMA OF MALIGNANT NEOPLASM ANEMIA IN PATIENTS WITH COLORECTAL CANCER

Colorectal cancer is an extremely urgent issue in modern medicine. This disease is often complicated by anemia, which has specific pathogenetics mechanisms of development and forms a mutual burden syndrome of diseases in cancer patients. The anemic syndrome is accompanied by the development of tissue hypoxia, which in turn activates the processes of oxidative stress and leads to increased release of biologically active compounds, in particular, biogenic amines. One of these is histamine. Its high concentrations cause spasm of the arterioles, which exacerbates tissue hypoxia. We have examined (n=153) patients with colorectal cancer without anemia, (n=75) patients with colorectal cancer complicated bymalignant tumor anemia, and (n=53) patients with iron deficiency anemia. The content of plasma free serotonin fractions was determined by the fluorometric method proposed by Mikhailychenko B.V., Vydyborets S.V. (1999). The patients with iron deficiency anemia and malignant tumor anemia have shown to have a significant increase in plasma free histamine, compared with the control group and the group of patients with colorectal cancer with out anemia. Plasma free histamine was increasing together with the severity of anemia. The article discusses the feasibility of using the content of plasma free histamine, as an option, to assess the state of compensation of secondary metabolic disorders in iron deficiency anemiaand malignant tumor anemia during treatment and its possible differential diagnostic value.

MODERN CONCEPTS ON THE ROLE OF HYPOXIA IN THE DEVELOPMENT OF TUMOR RADIORESISTANCE

The purpose of the study was to systematize and summarize modern ideas about the role of hypoxia in the development of tumor radioresistance.Material and Methods. PubMed, eLibrary and Springer databases were used to identify reviews published from 1953 to 2020, of which 57 were selected to write our review.Results. Radiation therapy is one of the most important components in cancer treatment. The major drawback of radiation therapy is the development radiation resistance in cancerous cells and secondary malignancies. The mechanisms of cancer radioresistance are very complicated and affected by many factors, of which hypoxia is the most important. Hypoxia is able to activate the mechanisms of angiogenesis, epithelial-mesenchymal transformation and contribute to the formation of the pool of cancer stem cell, which are characterized by chemo- and radioresistance. In turn, the severity of hypoxia largely dependent on tumor blood flow. Moreover, not only the quantitative but also the qualitative characteristics of blood vessels can affect the development of tissue hypoxia in the tumor.Conclusion. A comprehensive assessment of the severity of hypoxia, as well as characteristics of angiogenesis and EMT can contribute to a better understanding of the mechanisms of development of cancer radioresistance.

Clinicopathogenetic features of cardiovascular system affection in influenza patients with hypertensive reaction revealed for the first time

Aim. To study the state of central hemodynamics, oxygen metabolism and tissue blood flow in patients with influenza who suffered from hypertensive reaction detected for the first time, in dynamics of infectious process.
 Materials and methods. At Perm Regional Clinical Infectious Hospital, 65 patients with influenza underwent a deepened study of cardiovascular system: central hemodynamics and local blood flow.
 Results. While studying the central hemodynamics, there was detected the increased general peripheric vascular resistance without normalization during the follow-up period. Investigation of gas exchange showed decrease in tissue oxygenation, vasodilatation and tissue blood flow.
 Conclusions. Among patients with influenza, the oxygen transport system functions in a tense regime. In dynamics of infectious process and after the disease, the following is observed: development of tissue hypoxia, decrease in local blood flow tempo and elevation of general peripheric vascular resistance.

Контроль нітратів у продуктах рослинного походження

The issue of food safety and quality control is a top priority for every country. Owing to the intensive use of chemicals and preparations during the cultivation of crops of plant origin, there are cases (25-70%) when in the products sold, the content of nitrates is much higher than the norms. Consumption of such products can provoke deterioration in overall health, as exposure to high doses of nitrates leads to the development of tissue hypoxia in humans and inhibits oxidative phosphorylation. Chronic forms of nitrate poisoning due to oxygen starvation of organs and tissues, which is accompanied by impaired metabolism, reproductive function, suppression of immunity. These research results indicate the urgency of the control of nitrates in plant products consumed by the population of Ukraine. The purpose of the study was to establish the exceedance of the permitted levels of nitrate content in plant products that were tested at the State Research Institute for Laboratory Diagnostics and Veterinary Expertise during 2018-2019. Materials and methods. The analysis of the obtained data was carried out on the basis of the results of studies of nitrate content in samples of plant products, which were tested at the laboratory for determination of veterinary preparations and contaminants of the Research Chemical-Toxicology Department of the State Institute for Scientific and Technological Research during 2018-2019. Studies on the nitrate content were performed by ionometric method according to the current DSTU 4948: 2008 Fruits, vegetables and products of their processing. Methods for determining nitrate content. Results. The analysis of the results of the research conducted during 2018-2019 shows that in all types of studied plant products revealed exceedance of the maximum permissible levels (MPL) of nitrate content. It should be noted that a comparative analysis of the data obtained in 2018-2019 indicates the dynamics of an increase in the number of tested plant products with an excess of MPL of nitrates from 18 to 22%. Excess nitrates in plant products in 2018 were found to be more commonly found in beet, strawberry and carrot samples in 2018, and in 2019 in zucchini, cabbage and cucumbers. Probably, the harvesting of vegetables, from the data of the studied samples, was carried out in the early stages of plant vegetation. It is known that nitrates are most intensely absorbed by plants during the development of stems and leaves, not during the period of full maturation. Probably because of these samples of vegetable products the excess of MPL of nitrates was determined, which indicates that the vegetables are not suitable for consumption, since they can potentially cause toxic effects on the human body.

How much apoptosis does carbon monoxide poisoning cause? Primary clinical soluble TWEAK protein level study.

Carbon monoxide (CO) is an important cause of deaths via poisoning. CO poisoning causes inhibition of O2 transport and development of tissue hypoxia, which then causes cell apoptosis. A significant indicator of cell apoptosis, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) protein, is important for the stimulation of apoptosis. The primary purpose of this study is to determine whether apoptosis occurs during acute CO poisoning and to show that sTWEAK protein is an indicator of apoptosis that can be analyzed as a marker in the peripheral blood sample. The secondary aim is to determine the diagnostic and prognostic values of sTWEAK protein. The study was performed prospectively on 43 patients with CO poisoning and 30 healthy volunteer control individuals. The anamneses were taken from all patients, who also underwent physical examination. Complete blood count, biochemical markers, cardiac enzymes, and arterial blood gas measurements were analyzed. All the patients' sTWEAK protein levels were also analyzed. The sTWEAK protein level of patients with CO poisoning was 2278 pg/mL (1197-7234), while the level of the control group was 1609 pg/mL (310-3721). The patients' sTWEAK levels were significantly higher than the controls (area under the curve: 0.77 (0.66-0.89); p < 0.001), and the cutoff value was determined as 1895.50 pg/mL. The cutoff level had a sensitivity of 74.4%, a specificity of 76.7%, a positive predictive value of 82.0%, and a negative predictive value of 67.6%. sTWEAK is a significant indicator of apoptosis in CO poisoning that can be analyzed in the peripheral blood. However, further clinical trials are needed in terms of prognostic criteria.

Аcid resistance and population structure of erythrocytes in trotter horses during and after exercise

Regular physical exercise improves the cardiovascular system function, increases energy metabolism and antioxidant protection, provides greater muscle strength and physical endurance. However, exhaustive physical exercise can cause oxidative stress. During intense physical exercise, erythrocytes become more vulnerable to oxidative damage due to action of active oxygen forms, high concentration of polyunsaturated fatty acids. Physical loading of horses is accompanied by the development of tissue hypoxia, so one needs to study in detail changes of hematopoiesis indices, responsible for providing oxygen to tissues. When monitoring animal health, blood tests will detect a disease in early stages, because blood is a sensitive indicator of metabolic disorders, both of physiological and pathological body conditions. The purpose of present study was to examine changes of some hematopoiesis indicators (RBC, Hb, HCT, MCV, MCH), acid resistance of erythrocytesand population structure in trotting horses due to workloads of 1,600 m trot races (at rest, after race, after 90 min). In total, 20 clinically healthy horses of Orlovska and Russian trotting breeds, aged 2–3 years, were used in the study. The experimental animals included 5 mares, 15 stallions. All horses had active training. The horses were divided into two groups. The first animal group included animals that showed high results (2 min 04 s – 2 min 21 s); the second had trotters that covered the distance with worse time (2 min 28 s – 2 min 41 s). The erythrocyte couint in the leader horses after the loading increased, in the outsider horses it fell. After rest the leader horses’ erythrocytes returned to their original values, in the outsider horses they did not change. The outsider horses’ hemoglobin level after loading was lower than in the leader horses. The leader horses had higher hemoglobin content after rest (by 11.0% as compared with the values before the loading). The outsider horses had lower hemoglobin content. The leader horses hematocrit value increased, in the outsider horses ‒ decreased. The leader horses’ MCV after the loading was reduced, however after rest it recovered. The outsider horses showed MSV increase during the whole study period. The MCH in the leader horses did not change over the entire research period, in the outsider horses – it increased. The animals that showed better results, had an increasing number of “mature” and “old” erythrocytes due to their elimination from the depot. However, the outsider animals had an increasing number of “young” erythrocytes, resistant to hemolysis, but they were not able to provide tissues with needed oxygen.

Tissue oxygen exchange and oxidative processes in long-livers: Age-related peculiarities

The age-related peculiarities of tissue-oxygen exchange and oxidative processes in long-livers who were assumed to be physiologically aging individuals have been studied. Tissue oxygen served as the indicator of tissue oxygen exchange, which was measured by the polarographic method in the subcutaneous cellular tissue of the forearm while performing 10-min oxygen inhalation tests (with a spontaneous oxyhemogram recording) and a 10-min clamping of forearm vessels. This approach presents the opportunity to evaluate oxygen delivery and uptake. In order to quantitatively characterize oxidative processes, vacat-oxygen was assessed in the blood and urine, and the underoxidation coefficient proposed by Muller was estimated. It was established that the intensity of tissue respiration slows down, the amount of underoxidized products in the blood and urine rises, and the underoxidation coefficient increases with aging. The age-related decrease in the intensity of tissue respiration in subcutaneous cellular tissue indicates the development of tissue hypoxia due to reduced activities of enzymes that participate in the oxygen exchange process. The age-related reduction during tissue perfusion results in the formation of circulatory hypoxia, and contributes significantly to the formation of tissue hypoxia. These changes in oxygen exchange and oxidative processes in tissue detected for long-living individuals generally correspond to those seen in individuals aged 80–89. This finding makes it possible to speak on physiological aging in long-livers.

Effect of Cerebral Perfusion Pressure on Cerebral Cortical Microvascular Shunting at High Intracranial Pressure in Rats

Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the transition to MVS flow at high ICP. Rats were subjected to progressive, step-wise increases in ICP of up to 60 mm Hg by an artificial cerebrospinal fluid reservoir connected to the cisterna magna. CPP was maintained at 50, 60, 70, or 80 mm Hg by intravenous dopamine infusion. Microvascular red blood cell flow velocity, BBB integrity (fluorescein dye extravasation), and tissue oxygenation (nicotinamide adenine dinucleotide) were measured by in vivo 2-photon laser scanning microscopy. Doppler cortical flux, rectal and cranial temperatures, ICP, arterial blood pressure, and gases were monitored. The CAP/MVS ratio increased (P<0.05) at higher ICP as CPP was increased from 50 to 80 mm Hg. At an ICP of 30 mm Hg and CPP of 50 mm Hg, the CAP/MVS ratio was 0.6±0.1. At CPP of 60, 70, and 80 mm Hg, the ratio increased to 0.9±0.1, 1.4±0.1, and 1.9±0.1, respectively (mean±SEM; P<0.05). BBB opening and increase of reduced form of nicotinamide adenine dinucleotide occurred at higher ICP as CPP was increased. Increasing CPP at high ICP attenuates the transition from CAP to MVS flow, development of tissue hypoxia, and increased BBB permeability.

Oxygen Transport Impairments in Miners with Ischemic Stroke-Induced Comas

Objective: to study oxygen transport impairments in ischemic stroke-induced coma in miners who have been doing underground work for more than 10 years. Subjects and methods. A prospective clinical study was conducted in 48 patients with coma caused by ischemic stroke. Group 1 included 12 miners. Group 2 comprised 36 men not working in coal miners. The groups did not differ in age, disease severity, and admission time. However, the group of miners had a higher incidence of pulmonary complications and therefore higher mortality rates. Comprehensive examination was performed and oxygen delivery index (DO2I), oxygen consumption index (VO2I), oxygen extraction ratio, and arteriovenous oxygen difference were calculated in all those admitted to hospital. Results. In ischemic stroke-induced comas, vasoconstriction resulted in the development of circulatory hypoxia with low DO2I. Then on day 3 respiratory and tissue hypoxia developed in the group of those who had a length of underground service. The relationship between DO2I and VO2I found in the miners suggests that impaired lung oxygenizing function was concurrent with oxygen transport system tension. The fact that there was no significant relationship of the oxygen saturation of hemoglobin in venous blood to VO2I in the miners had a high probability of indicating the development of tissue hypoxia. Such relationships were absent in the patients without underground length of service. Conclusion. The miners with an underground service length of 10 years or more and ischemic stroke-induced comas were found to have rapidly developing, more marked and long-term impairments of central hemodynamics, pulmonary oxygenizing function and hence the oxygen transport system as compared to those with no length of underground service. All the above characteristics are due to the lowered reserve capacities of the cardiovascular irnd respiratory systems upon long-term exposure to poor working conditions. Key words: ischemic stroke, oxygen transport, length of underground service, miner.

Fundamentals of multilevel mesomechanics of nanostructural transitions in erythrocyte membranes and their destructions in interaction with stress hormones

Stress hormones (cortisol, adrenaline, noradrenaline) are capable for nonspecific binding with erythrocyte membranes thus initiating structural-phase transitions in them. The binding constants for cortisol, adrenaline and noradrenaline are respectively 1.23·106, 6.3·106 and 1.7·106 M−1. The amount of bound hormones varies in the range 10∼10-10∼n mole/mg of protein. The binding involves hydrogen bonds, hydrophobic bonds and electrostatic bonds. Active groups of hormones (amino-, imino-, methylamine-, keto- and hydroxy-groups) interact simultaneously with CO- and NH-groups of both proteins and phospholipids. These processes underlie structural-phase transitions in an erythrocyte membrane in its interaction with stress hormones. The structural-phase transitions result in complex protein-lipid domains of increasing structural order in the membrane. At the same time, water dipoles are displaced from the domains to adjacent regions and promote membrane loosening. The membrane microviscosity thus greatly increases in the regions of both protein-lipid interactions and lipid-lipid interactions. The increase in erythrocyte membrane viscosity hampers the motion of erythrocytes through capillaries, and as a certain critical threshold is approached, this contributes to the development of tissue hypoxia. The mesomechanics of structural-phase transitions and destruction in external fields of biological membranes and nanostructured solids are qualitatively alike.

HIF-1α antagonizes p53-mediated apoptosis by triggering HIPK2 degradation

Many human diseases are characterized by the development of tissue hypoxia. Hypoxia-inducible factor (HIF) is a transcription factor that regulates fundamental cellular processes in response to changes in oxygen concentration, such as angiogenesis, survival, and alterations in metabolism. The levels of HIF-1α subunit are increased in most solid tumors not only by low oxygen but also by growth factors and oncogenes and correlate with patient prognosis and treatment failure. The link between HIF-1α and apoptosis, a major determinant of cancer progression and treatment outcome, is poorly understood. Here we show that HIF-1α protects against drug-induced apoptosis by antagonizing the function of the tumor suppressor p53. HIF-1α upregulation induced proteasomal degradation of homeodomain-interacting protein kinase-2 (HIPK2), the p53 apoptotic activator. Inhibition of HIF-1α by siRNA, HIF-1α-dominant negative or by zinc re-established the HIPK2 levels and the p53-mediated chemosensitivity in tumor cells. Our findings identify a novel circuitry between HIF-1α and p53, and provide a paradigm for HIPK2 dictating cell response to antitumor therapies.

Dysadaptation mechanisms of the human's in Antarctic

Long-term complex monitoring medical-biological researches of the human's functional systems status at the prolonged stay in the conditions of isolation at the off-shore (coast) Antarctic station were focused on finding out of mechanisms of dysadaptative disorders development of integrative and oxygen-transport systems of organism in the absence of essential reduction of the oxygen content in atmospheric air. Work was based on the results of medical-biological studies, which were conducted with participation of the crew members of the Antarctic station Academician Vernadskiy (Vernadsky – 65° 14'43S; 64° 15'24W). The average age of examinees was 39,8±2,4 years (130 men). The medical-biological studies included the modern clinic-laboratory, functional, instrumental, biochemical, immunologic, genetic, statistical methods. The participants' examinations of the expedition were conducted before expedition, at a period of transatlantic transition, on Antarctic station (in mode of the monitoring by means of telemedical connection), after returning from expedition. In Antarctic the unique complex of physical, chemical, biological, of social, nature (the metheoheliogeophysical, biorhythmological, deprivation) factors, exceeding by power and duration, affect a human. Long influence of these factors brings to the adaptation processes disorders and dysadaptative development. It is shown that the mechanisms of dysadaptative disorders of oxygen-transport systems of the human organism at the long stay under the influence of the complex of extreme factors of Antarctic expedition developed on the background of the chain neurohumoural, neuroimmune, metabolic, celluar dysfunctions, which indicated on the presence of signs of long stressful condition (the stress-syndrome) that brings to adaptative mechanisms exhaustion of compensation and requires using the methods of correction. At the long stay of a human on the coast Antarctic station, there was revealed the seasonal dynamics of adaptative-dysadaptative rebuildings of regulative and oxygen-transport systems, there was revealed the presence of signs of stressful status and development of tissue hypoxia. It was shown the pathogenic mechanisms of development of dysadaptative disorders of integrative systems (change in cerebral electrogenesis, the activation of sympathoadrenal system, immune malresistance),respiratory, circulatory and hemic mechanisms of regulation of organism oxygen modes (the fall in efficiency and economy of the regulation mechanisms). It is shown the role of biorhythmologic and heliophysical factors of environment in development of dysadaptative disorders. It is for the first time fullfilled the genetic typization of the participants of Antarctic expedition on the presence of an allele polymorphism of specific genetic factor (hypoxia inducted factor - HIF-1α). The significance of such human gene HIF-1α polymorphism is studied in correction to development of adaptative-dysadaptative rebuildings of the functional systems at a continuous stay in Antarctic. It is shown the stabile reduction of regulation mechanisms of an organism oxygen modes under influence of Antarctic factors and hypoxia loading among winterers with C/T polymorphism of the gene HIF-1α, that has prognostic importance and opens way to deepened study of the molecular mechanisms role in development adaptative-dysadaptative processes in a human in extreme conditions.

Vascular involvement in the pathogenesis of idiopathic inflammatory myopathies

The identification of the exact role of the involvement of the vascular system in the pathogenesis of idiopathic inflammatory myopathies (IIMs) has been the task of several scientific investigations during the recent years. The observations that microcirculatory disturbances might play a major—if not perhaps the primary—role in IIMs have gained wide recognition among the scientific community and led to different experimental and clinical attempts to study the role of microvessels in IIMs. During the past years, the ‘Vascular Hypothesis’ of the pathogenesis of IIMs has been co-developed in our laboratory supported by experimental and clinical data. This hypothesis is based on assumptions that phenotypically altered microvessels might affect the local circulation of the muscle and hence lead to the development of tissue hypoxia and metabolic alterations. Subsequently, local hypoxia in muscle tissue could lead to muscle weakness and muscle fatigue, which are the most prominent clinical signs in IIM patients. This hypothesis is further supported by the reported benefits of physical exercise and associated molecular alterations in muscle in patients with IIMs. This review will highlight some of the most important findings that elucidate the role of vascular endothelial cell dysfunction and hypoxia in the pathogenesis of IIMs.