Finding possible diagnostic markers for differentiating benign and malignant thyroid tumors on example investigate of rheological properties1.

BACKGROUND: The functioning of the thyroid gland is a multi-component process that in some conditions may undergo alterations. The thyroid gland is part of the endocrine system that produces the iodine-containing hormones thyroxine and triiodothyronine. Thyroid hormones, control metabolism and energy, growth processes, maturation of tissues and organs, regulation of blood flow, and, therefore, providing vital functions of the body. The role of thyroid hormones in the regulation of blood flow is determined by the intensity of their production and the quantity in the blood. Presumably, in case of oncological and non-oncological diseases of the thyroid gland, the fluidity of the blood, which depends on the rheological properties, will be different. OBJECTIVE: Our aim was investigating rheological characteristics for studying of changes of rheology in patients with thyrotoxicosis, with benign tumor pathology of the thyroid gland, with thyroid cancer and finding possible diagnostic markers for differentiating benign and malignant thyroid tumors. METHODS: In this regard, we examined, using modern methods accepted in clinical practice, a standard list of recommended diagnostic tests in the group of patients (thyrotoxicosis: n = 25; benign tumor: n = 47), thyroid cancer: n = 35) and control group (n = 15), and with new original methods, parameters that describe the rheological properties of the blood, such as blood rheological index, volume, thickness, surface area of erythrocytes, erythrocyte aggregation index, deformation index, plasma viscosity, hematocrits. RESULTS: Against the background of relative changes in the studied values, it is necessary to pay attention to the fact that erythrocyte aggregation in patients with a benign form and control, as well as in patients with a malignant form and control, differ significantly from each other, in addition, there is a significant difference between aggregation in the group of patients with benign and control aggregation. malignant forms of the disease. It is significant that aggregability differs in patients with thyrotoxicosis and in controls. This indicates that erythrocyte aggregation is particularly informative. The blood rheological index most clearly demonstrated the difference between benign and malignant forms of the disease. Significantly changed compared to control in various forms of thyroid diseases. CONCLUSION: Additional diagnostic markers for differentiating benign and malignant thyroid tumors may be consideredeerythrocyte aggregation index and blood rheological index.

Impact of different severity hyperglycemia on erythrocyte rheological properties1.

BACKGROUND: The triad "insulin resistance, prediabetes, diabetes" is three independent neologies with characteristic features and development. In addition, each are characterized by progression and the possibility of transition from one form to other. Due to the fact that diabetes is one of the common diseases associated with high rates of disability, it is necessary to improve diagnostic methods and educational regimens for successful prevention and treatment of the disease. OBJECTIVE: We investigated Band 3 protein (B3p) level, osmotic resistance of erythrocytes, the total antioxidant activity (TAA) of blood serum, level of HbA1 in group patients with insulin resistance (IR), prediabetes, and Type 2 Diabetes Mellitus (T2DM) and comparative with health control group. METHODS: We used original, accurate research methods that measure the essence of the studied quantities. RESULTS: Disruptions of glucose and insulin homeostasis ay lead to the initiation of oxidative stress (in our study demonstrated by a decrease of TAA of blood serum) increased redox-sensitive PTP activity and aberrant band 3 phosphorylation, potentially leading to reduced erythrocyte deformability. At the same time glycation of Hb during T2DM may affect its cross-link with membrane proteins, in particular with B3p, and although appears to limit its cross-linking and decrease its clusterization ability, induces alterations in the cytoskeletal matrix, and thereby decrease erythrocytes' osmotic resistance making them more susceptible to hemolysis. CONCLUSIONS: The osmotic resistance of the erythrocytes can be used as a sensitive marker for the detection of the early stages of hyperglycemia (prediabetes). This set of clinical trials will make it possible to identify diseases that make up the triad at an early stage. Early detection of disorders and continued research in this direction will help in the development of a diagnostic scheme for the prevention of such patients. Based on our data, research into anti-oxidation drugs is very important. With the help of the array of studies described in the article and antioxidant treatment, the likelihood of successful treatment will increase.

MONITORING OF HEMORHEOLOGICAL PARAMETERS IN PATIENTS WITH ATRIAL FIBRILLATION (INITIAL DATA).

The goals of this project were to determine how hemodynamics and hemorheological change in patients diagnosed with different forms of atrial fibrillation; also, how relievers of changes in fibrinogen monitoring in patients with permanent, persistent, paroxysmal forms of arrhythmias. There was examined 30 patients (the average age of patients 65). Patients and control groups have been tested the following studies: index of erythrocytes aggregability, deformability, plasma viscosity to evaluate the blood rheological parameter, also -Fibrinogen to determine of coagulation condition. The Index of the Erythrocytes aggregation was done with the system of textural analyzes. These new innovative methods "Georgian Technique" is created by Georgian scientists and they are famous in the world as direct, numeral and exact. The index of the deformation of the erythrocytes was done with filtration method. Plasma viscosity was measured in the capillary viscosimeter in 370 C. According to the obtained data patients with atrial fibrillation have the same conditions of rheological and coagulation systems, despite of the forms of the atrial fibrillation. And it is different compared to the control group. In the statistical processing of the total row of fibrinogen, the patients were divided into 3 categories. As it turned out fibrinogen and Index of erythrocytes aggregation are in a linear relationship. The quantity of fibrinogen and of erythrocytes aggregation increase simultaneously and the greater the sequential number of the category is, the changes are more pronounced. However, the change/variability of each biological parameter, as shown from our data, is not uniform and linear. The obtained results clearly illustrate the existence of two parallel mechanisms in the body. These are on the one hand the systems of coagulation, anti-coagulation and fibtinollysis. These processes are in a state of the weighted condition, and they are characterized by dynamic equilibrium. On the other hand, the rheology system, which involves the combination of blood flow, blood velocity, vascular stiffness / elasticity, is characterized by one direction going on, with the adequacy and non-existing antipodal mechanisms. The hemorheological system does not have a physiologically balanced opposing anti-rheological system. All of this generate that the hemorheological status is very important in the development and formation of some disease. The arrangement of a rheologycal system is taking preventive character. On the one hand, the rheologycal system is a consolidation of diagnosis and evaluation of the mechanisms. Also, it is the treatment target. Normalization of them is very important in the therapeutic standpoint of the individual.

Hemorheological, microvascular and hemodynamic disorders during coronary heart disease.

Significance of the hemorheological disorders in development of acute vascular syndromes is presently well known, but their role in pathogenesis of chronic coronary heart disease has not been yet sufficiently analyzed. Aim of the present study was the investigation of the relationship between the hemorheological, vascular and hemo-dynamic factors responsible for development of the coronary heart disease. We investigated 64 patients with coronary heart disease of the functional classes I-IV with and without the heart failure. For evaluation of the hemorheological disorders we investigated its most significant symptom, the erythrocyte aggregability, with the "Georgian technique" that provided us with direct and quantitative data. We investigated also the tone of the hand's resistance arteries with an original non-invasive technique based on measurement of the flow velocity changes in the patients and in the healthy controls radial arteries by using the Doppler technique during standardized postischemic hyperemia. Echocardiographically we studied the standard characteristics of left ventricular function (systolic and diastolic volume, its mass and ejection fraction). ECG by standard leads and the blood pressure were investigated in all patients. We found that the rheological disorders are manifested in the early stages of the disease before its functional manifestation. The most pronounced hemorheological disorders were in evidence in the patients with unstable angina and heart failure. As to the arteriolar resistance index, it was increased only in 45 per cent of all the investigated patients and no significant difference between the patients with the heart failure and without it was found. There was a negative relationship between erythrocyte aggregability and the ejection fraction of the left ventricle and the positive correlation between erythrocyte aggregability and left ventricle hypertrophy (p<0.01). We concluded that the blood rheological disorders represent themselves a factor that plays a significant role in pathogenesis of the coronary heart disease. They are predictors of the disease and not only risk factors as it is generally believed. Measurement and correction of these disturbances in its early stages have a high clinical significance.

Comparison of erythrocyte aggregability changes during ischemic and hemorrhagic stroke.

The aim of this work was to perform a comparative investigation of erythrocyte aggregability changes in the peripheral and cerebral circulation during ischemic and hemorrhagic stroke. Subjects of the present study were patients with ischemic brain infarcts (14 patients) and with hemorrhagic stroke (21 patients) from the Intensive Care Unit of the Institute of Neurology and Neurosurgery. The blood samples were obtained from the following blood vessels: the common carotid artery carrying blood to the primarily damaged brain hemisphere, both jugular veins carrying blood from the primarily damaged and the contralateral hemispheres, as well as from the cubital vein to obtain specimens of the systemically circulating blood. Erythrocyte aggregation was evaluated by using the "Georgian technique". We found that the RBC aggregation indices increased in both the regional as well as the systemic circulation of the hemorrhagic stroke patients as compared to ischemic stroke patients. The results of the present study demonstrate different changes of erythrocyte aggregation in ischemic and hemorrhagic stroke patients. Therefore, the role of blood rheological properties in their pathogenesis seems also to be different.

About spread of local cerebral hemorheological disorders to whole body in critical care patients.

PURPOSE: The aim of the present pathophysiological studies was elucidation of the feasible mechanism of spread of the blood rheological disorders from the cerebral to systemic circulation, and vice versa. METHODS: The investigation was carried out in the critical care patients with the brain tissue damage related to stroke (cerebral ischemic infarcts as well as parenchymatous and subarachnoid hemorrhages). The applied diagnostic techniques provided us with valid and quantitative data revealing the degree of the red blood cell aggregability, the value of local hematocrit, and the blood plasma viscosity in the cerebral and systemic circulation. In addition, rabbits experiments were carried out for analysis of the hemorheological disorders associated with the brain damage. RESULTS: Despite the local character of the patients primary brain damage, the hemorheological disorders were found regularly spread not only over the cerebral hemispheres, but even also the systemic circulation. Under such conditions they might cause the generalized brain tissue damage and play significant role in the subsequent damage-cascade of the whole brain. In addition, the rabbits experiments demonstrated pronounced hemorheological disorders in the cerebral cortex capillaries: increase of their numbers with RBC enhanced aggregation and blood stasis, as well as with lowering of the RBC deformability in the narrow capillary lumina. These changes befell simultaneously with increase of water contents in the cerebral tissue evidencing for edema development in the brain. CONCLUSION: Local cerebral hemorheological disorders might spread over the whole brain via the systemic circulation, thus promoting a generalized brain damage and being responsible for the critical state of the patients.

Hemorheological disorders and arteriolar resistance during ischemic heart disease.

It could be conjectured that the hemorheological disorders are involved in development of the ischemic heart disease. But this fact was so far insufficiently cleared up. The present studies were carried out in patients with various forms of chronic ischemic heart disease. We investigated the most significant factor of rheological disorders in the microcirculation, the erythrocyte aggregability, with a technique that provided us with the direct and quantitative data. Simultaneously we investigated in the same patients the tone of the resistance arteries of the hand with an original non-invasive technique. We found that the erythrocyte aggregability increased almost twice in the blood of investigated patients as compared to the healthy control group. The aggregability was positively correlated with severity of the disease. The most pronounced hemorheological disorders were found in the patients with the heart failure. As to the arteriolar resistance index, it was increased only in 45 percent of all the investigated patients and no significant difference between the patients with the heart failure and without it was found available. We concluded that the blood rheological disorders represent themselves a factor that plays a significant role in pathogenesis of development of the heart disease.

Blood rheological abnormalities in the microcirculation during experimental traumatic shock.

OBJECTIVE: To find whether the principal indices of blood rheological disorders related to the microcirculation undergo drastic changes during the traumatic shock. METHODS: RBC aggregability and deformability, as well as the systemic hematocrit, were assessed in white laboratory rats with the techniques that provided us with direct and quantitative data. RESULTS: We found that in the experimental animals the RBC aggregability was sharply increased, the RBC deformability significantly decreased, while the systemic hematocrit underwent considerable lowering during the traumatic shock. CONCLUSION: The blood rheological properties are significantly disordered during development of the traumatic shock.

Effect of nitric oxide initial blood levels on erythrocyte aggregability during 12 hours from ischemic stroke onset.

The aim of study was the investigation of blood nitric oxide (NO) and nitrates (NO2) levels in 12 hours of ischemic stroke onset and establishment of correlation of these data with erythrocyte aggregability and initial ischemic lesion size. 48 patients, aged 45 to 70 years, 26 female, 22 male were investigated. Glasgow Coma Scale (GCS) and National Institute Health Stroke Scale (NIHSS) assessed initial neurological impairment. Patients were divided in mild and severe stroke groups. Control comprised 20 healthy individuals. Ischemic lesions were evaluated on conventional MRI scans. NO levels were measured by electron paramagnet resonance (EPR) method. NO2 levels were defined by spectrophotometer method. Erythrocyte aggregability index (EAI) was measured by sound method [Biorheology 30(2) (1993), 153-161]. Pearson correlation and multivariate model of logistic regression was applied. Significant negative correlation was established between NO initial blood levels and the EAI (r=-0.75; p<0.001), as well as between blood NO2 and NO initial levels and ischemic lesion size (r=-0.79, p<0.01; r=-0.61, p<0.02, respectively). Endothelialy derived NO correlates with erythrocyte aggregability and probably has a positive impact on restoration of cerebral blood flow in the initial stage of acute brain ischemia.

Lipid peroxidation in the erythrocytes under condition of their increased aggregation.

The aim of the present study was investigation of the lipid peroxidation changes within the erythrocytes under conditions of increased RBC aggregation. This latter was produced both in the in vitro and in vivo conditions by the addition of Dextran T-500. For the in vitro studies blood samples were taken from the cubital veins of 15 healthy subjects. During the in vivo studies 10 ml of the 10 percent Dextran T-500 solution was administered intravenously in six chinchilla rabbits. Another six animals were treated with rheopolyglucyne. The RBC aggregation in blood was investigated with the "Georgian technique". The malondialdehyde (the end product of lipid peroxidation) was determined in all cases by its reaction with thiobarbituric acid. We found that in the in vitro conditions, as well as in the in vivo studies, the lipid peroxidation was significantly increased in the erythrocytes during the enhanced RBC aggregation induced by addition of Dextran T-500. Therefore we suppose that the elevated RBC aggregation cause an increase of cell's lipid peroxidation and it is possible to think that appropriate prooxidant: antioxidant balance is shifted toward the pro-oxidants in the erythrocytes.

Blood rheological properties and lipid peroxidation in cerebral and systemic circulation of neurocritical patients.

The present study was aimed at investigating the red blood cell (RBC) aggregation and the parameters of lipid peroxidation - malondialdehyde (MDA) and MDA + 4-hydroxyalkenals (HAE) - in the blood of critically deteriorated stroke patients (brain infarcts, parenchymatous and subarachnoid hemorrhages) and in the control group. Measurements were made in blood samples from the common carotid artery, the both internal jugular and cubital veins. The RBC aggregation index was found to increase by about 80 per cent in both the cerebral and systemic circulation as compared to the control blood samples. MDA content appeared also significantly higher in the blood flowing out of the damaged hemisphere of the neurocritical patients as compared to the control group. In the blood flowing out of the damaged hemisphere of the neurocritical patients MDA as well as MDA + HAE content significantly exceeded the values found in blood samples of the jugular vein of the contralateral hemisphere, carotid artery and the cubital vein. The results of this study suggest a certain interdependence between the blood plasma lipid peroxidation and the RBC aggregation in the brain vessels following its damage.

Comparative values of erythrocyte aggregability versus other indices of hemorheological disorders in patients with ischemic brain infarcts.

The aim of the present study is comparison of changes of principal hemorheological factors responsible for blood flow disorders in the microcirculation in patients with ischemic brain infarcts. It was found that in venous blood samples the erythrocyte aggregability (examined with a direct, highly sensitive, quantitative technique) was considerably more increased (by mean of 120%) than the blood plasma fibrinogen contents, blood plasma viscosity, and hematocrit which increased only by 23.7%, 7.4% and 3.6%, respectively, as compared to the same hemorheological factors in the healthy controls. These results led us to the following conclusion: among the other tests the enhanced erythrocyte aggregability, when measured with an appropriate technique, is the best diagnostic indicator of hemorheological derangements during development of the ischemic brain infarct.

Microcirculatory stasis induced by hemorheological disorders: further evidence.

OBJECTIVE: Reinvestigate the microcirculatory alterations immediately responsible for blood rheological disorders and blood stases, which are related to red blood cell (RBC) aggregation in capillaries. METHODS: Blood rheological disorders were produced by significantly intensified intravascular red blood cell aggregation in the intestinal mesentery of Wistar rats and in the cerebral cortex of Chinchilla rabbits, either systemically (by intravascular administration of high molecular-weight dextran) or locally (by increase of high-molecular compounds in blood plasma inside individual or groups of capillaries). RESULTS: Under conditions where the microvascular lumina were not decreased and the arteriolovenular pressure gradients got even higher, the significantly enhanced intravascular RBC aggregation resulted in the slowing down of blood flow in the microvessels to a full stop. CONCLUSION: A significant increase in microvascular RBC aggregation results in local hemorheological disorders, which is, in all probability, related to derangement of the blood-flow structuring in microvessels.

Kinetics of beneficial effect of pentoxifylline on persistent forms of arterial hypertension.

In some hypertensive patients a high level of arterial pressure proved resistant to the effect of Ca-antagonists. However, the addition of therapeutic doses of Pentoxifylline caused a significant decrease of blood pressure. The arterial pressure changes were found to be correlated with the index of erythrocyte aggregability (investigated using a highly sensitive "Georgian technique") in these patients. Thus, a pathogenetic link between blood pressure and hemorheological disorders could be conjectured. For a better understanding of the mechanism of these events the direct effect of Pentoxifylline on erythrocyte aggregability was investigated in vitro by using the blood samples of hypertensive patients possessing hemorheological disorders. The obtained results showed that the effect of Pentoxifylline (in therapeutic doses) was direct and that the dose-effect dependence was linear. From the obtained results we concluded that the beneficial effect of Pentoxifylline in hypertensive patients resistant to Ca-blockers is attained by eliminating the immediate cause of blood rheological disorders, the enhanced erythrocyte aggregability.

Blood flow structuring and its alterations in capillaries of the cerebral cortex.

Various manifestations of blood flow structuring were investigated in rabbit cerebral cortex capillaries, which possess the most narrow lumina of all parts of the body. Blood flow structuring in the capillaries was characterized by the presence of a stable and comparatively large parietal plasma layer, which changed insignificantly under control and ischemic conditions, but disappeared when blood stasis developed inside the capillaries. The axial core of the blood flow in the capillaries, which occupied almost two-thirds of the intracapillary volume under normal conditions, consisted of significantly deformed (stretched along the microvessels' axes) and nonaggregated erythrocytes. During ischemia the shape of the erythrocytes did not change appreciably; only the blood plasma intervals between them increased significantly, demonstrating reduction of the local hematocrit. During primary blood stasis caused by enhanced intravascular erythrocyte aggregation, typical blood flow structuring became significantly disturbed: red cells filled the whole, or almost the whole, capillary lumina and did not leave visible space for plasma inside the microvessel lumina. We concluded that normal blood flow structuring is a deciding factor in the blood rheological properties of microvessels. Its disturbance, caused by fast accumulation of erythrocytes in the capillary lumina, results in blood rheological disorders and in a slow down to a full stop of the blood flow, despite a preserved arteriolovenular pressure difference.