Effect of Xe/O2 Inhalation on Hemostasis in Experimental Thromboplastin Pneumonitis.

We studied the effectiveness of Xe/O2 mixture inhalation (30% Xe and 70% O2, 20 min for 5 days) in a model of experimental thromboplastin pneumonitis. Inhalation of the studied mixture decreased the intensity of the inflammatory process in the lung tissue assessed by the temperature response of animals, changed lung weight and lung weight coefficient. At acute stage of pneumonitis, an increase in xenon consumption was recorded due to its retention in the gas exchange zone and a natural decrease in oxygen consumption due to partial alveolar/capillary block. The formation of pneumonitis was accompanied by a pronounced procoagulant shift in the regulation system of the aggregate state of blood. The Xe/O2 inhalations ensured physiologically optimal levels of prothrombin and activated partial thromboplastin time against the background of a moderate decrease in fibrinogen level throughout the experiment. At the same time, the activity of the natural anticoagulant antithrombin III increased from day 5 to day 14.

Effect of Paclitaxel on the Hemostatic Potential of the Blood in the Experiment.

The duration and severity of prothrombotic effects of the maximum tolerated dose of paclitaxel (40 mg/kg) were evaluated in intact outbred mice. Hemostasis was assessed before and on days 1, 2, 5, 7, 10, 15, 20, and 30 after a single injection of paclitaxel using standard coagulation tests (activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin III) and a "global" method, low-frequency piezothromboelastography. A pronounced prothrombotic effect of paclitaxel was revealed starting from the first day postinjection that consisted in intensification of fibrinogenesis up to the 7th day in parallel with activation of the anticoagulant mechanisms. On days 7-30 after paclitaxel administration, decompensation of its anticoagulant activity due to paclitaxel-induced damage to the endothelium was observed with the formation of a procoagulant status of the hemostatic potential of the blood. A single administration of the maximum tolerated dose of paclitaxel forms a powerful thrombogenic stimulus during the first week and provides a long-term/trace procoagulant shift in the hemostasis system (days 10-30).

Xenon-Induced Effects in Relieving Experimental Acute Respiratory Distress Syndrome.

The effects of inhalations of an oxygen-xenon (70%/30%) mixture were studied in two models of acute respiratory distress syndrome caused by intratracheal administration of 0.5 mg/kg LPS or 0.04 ml acidin-pepsin (pH 1.2). Inhalation of the oxygen-xenon mixture inhibited the development and reduced the intensity of the inflammatory process in the lung tissue, which was assessed by the dynamics of lung weight and body weight of animals: the therapeutic exposure decreased both parameters. It was found that the thrombogenic stimulus, pathognomonic for the development of acute respiratory distress syndrome, decreased under the effect of oxygen-xenon inhalations, while the level of natural anticoagulant antithrombin III increased.

Erythropoiesis-Stimulating Properties of Anthocyanin-Containing Complex from Sorbus aucuparia L. in Cytostatic Anemic Syndrome in Mice with Lewis Lung Carcinoma.

The results of studying the effect of the anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice with Lewis lung carcinoma against the background of doxorubicin administration were presented. It was shown that administration of the anthocyanin-containing complex from S. aucuparia L. to animals with the tumor prevented the development of anemic syndrome by promoting regeneration of the erythropoiesis after its depletion caused by single administration of a cytostatic agent.

Erythropoesis-Stimulating Properties of Anthocyanin-Containing Complexes in Cytostatic Anemic Syndrome.

We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S. aucuparia L. prevented the development of anemic syndrome by stimulating regeneration of the erythroid lineage of hematopoiesis after its devastation by single administration of the cytostatic.

Pharmacological Correction of Cisplatin-Induced Hemostatic Disorders.

A single intraperitoneal administration of cisplatin in the MTD to outbred female mice disturbed hemostasis and formed the procoagulant phenotype of hemostatic potential on days 7-10 culminating in a pronounced hypocoagulation on day 15. Hemostasis was corrected with warfarin and an extract containing furocoumarins composed of isopimpinellin (42.97%), bergapten (35.18%), and xanthotoxin (15.41%). The extract was standardized with gas chromatography-mass spectrometry, thin-layer chromatography, and HPLC. Furocoumarins and reference drug warfarin were administered intragastrically during 4 days starting on day 6 after the administration of cisplatin. Both furocoumarins and warfarin corrected hypercoagulation on days 7-10. On day 10, furocoumarins normalized coagulation, whereas warfarin resulted in hypocoagulation. On days 15-30, no effects of warfarin were observed. furocoumarins corrected hypocoagulation on days 15-20 with prolongation of this effect up to experimental day 30.

Changes in Hemostasis System in Outbred Female Mice with Cisplatin-Induced Procoagulant Status.

Procoagulant status was modeled in outbred female mice by single injection of cisplatin in a maximum tolerated dose and hemostasis parameters monitored over 30 days by methods of coagulogram and low-frequency piezothromboelastography (global test). Monitoring revealed waveform changes in the hemostatic potential: the structural and chronometric hypercoagulation recorded starting from the first day and attaining its maximum on days 5-7 was followed by hypocoagulation and returned to normocoagulation on day 30. This pattern reflects prolonged effect of cisplatin: formation of severe dysfunction of the endothelium providing the main anticoagulant pool of hemostasis (day 1) aggravated by disturbances of the plastic functions of the liver (days 15-20), and recovery (days 20-30).

Dalayed Effects of Antitumor Drug Paclitaxel on the Hereditary Material and Hemopoietic System of CBA Mice.

Paclitaxel in a single MTD of 40 mg/kg caused chromosome aberrations and genome changes (polyploidy) in the bone marrow cells of mice early and 3 months after the injection. The quantity of early precursors of erythropoiesis in the bone marrow decreased, as did their proliferative potential irrespective of the animal gender. Injection of paclitaxel in the MTD caused the development of bone marrow hypoplasia during the early period of observation (up to 14 days) and 3 months after injection.

Modification of the Myelotoxic and Antitumor Effects of Polychemotherapy by Polysaccharides from Tussilago farfara L.

The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.

[Age features peripheral link erythron rats and its status with experimental cardiosclerosis].

Studied the performance of the peripheral unit erythrone rats aged 4 months (1st group) 12 months (2nd group) and 24 months (3rd group). Each age group (n=20) consisted of 10 intact animals and 10 animals c postinfarction cardiosclerosis (PICS). In the group of animals 24 months of age was showed an increase in the number of erythrocytes in the absence of difference in the amount of reticulocytes. Expressed anisocytosis and decrease in hemoglobin synthesis in animals of this age group suggests that the age-related disorders maturation of erythroid cells. The development of post-infarction myocardial remodeling has not affected polycythemia typical for animals of older age group. At the same time a significant increase in the reticulocyte count of peripheral blood smears was observed for this group of animals. Development of PICS for animals extreme age groups leads to a smoothing interage differences, noted in the animals in the intact condition.

Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3.

We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.

Pathogenetic Evaluation of Dysfunction in the Erythron System of Experimental Animals during Modeling of Iron Deficiency Anemia in the Gestation Period.

We studied the dynamics of erythropoiesis in CBA mice during gestation against the background of treatment with iron-binding drug. The mechanisms of suppression of the bone marrow erythroid stem were evaluated. Administration of deferoxamine in a dose of 1 g/kg induced hypoplasia of the erythroid hemopoietic lineage. Suppression of bone marrow erythropoiesis manifested in a decrease of hemoglobin concentration and counts of reticulocytes, erythrocytes, and erythrokaryocytes. These changes were accompanied by a decrease in functional activity of erythropoietic precursors and secretion of erythropoietically active humoral factors by bone marrow myelokaryocytes. These data indicate that deferoxamine can be used for modeling of iron defi ciency anemia in pregnancy.

Study of Subchronic Toxicity of Relatox on Sexually Immature Animals.

Intramuscular injections of Relatox in therapeutic and toxic doses to young outbred laboratory rats for 14 days caused no changes in the peripheral blood and bone marrow parameters, serum biochemical parameters, and morphology of the major viscera. In the toxic dose, the drug caused local irritation (inflammation, atrophy, and sclerosis in muscle tissue). Regeneration processes started in muscle tissue 7 days after Relatox withdrawal.

[DYNAMICS OF BLOOD PRESSURE AND QUANTITY INDICES OF ERYTHROCYTES IN SHR IN EARLY PERIOD OF ARTERIAL HYPERTENSION FORMING].

The dynamics of arterial blood pressure and hematological parameters (RBC volume, RBC count, hematocrit) in young rats SHR and WKY strains in the period from the 5th to the 8th week after birth was investigated. At the age of 5 weeks, the levels of arterial blood pressure in rats studied strains were not significantly different. Starting from 6 weeks, systolic and diastolic blood pressure in SHR rats were significantly higher than the corresponding values of WKY rats of the same age. During the entire period of observation (from the 5th to 8th week) the number of red blood cells and hematocrit in SHR rats was significantly increased compared with the value of these parameters in WKY rats. Probably, an increased hematocrit can be one of the reasons of increasing the blood pressure in the early stages of hypertension development.

Quantitative Indexes of Leukocytes in Spontaneously Hypertensive Rats During Various Periods of Arterial Hypertension Development.

SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.

[Pharmacological correction of the cytogenetic effects of cisplatin].

Beginning with the first hours of experiments, cisplatin evoked an increase of chromosomal aberrations in CBA/CaLac bone marrow cells. Significant increase of structural infringements of chromosomes due to chromatid breaks was revealed in metaphase plates of murine bone marrow preparations through 24 h after cisplatin intraperitoneal introduction. In late terms of research (90th day), the high level of aberrations of chromosomes was retained. The most pronounced correction of cisplatin mutagenicity was achieved using a preliminary course of thiophan introduction.

[Hemodynamic and methabolic aspects of sodium nitroprusside pharmacodynamics during buccal administration in patients with arterial hypertension of cerebral ischemic genesis].

The authors presented in the article efficiency of new formulation of Natrium Nitroprusodum used buccaly in patients with cerebral-ischemic form of arterial hypertention and stage II hypertention. It has been shown both in an acute experiment and after monothrerapy having been used. The medication proved to have positive effect on brachiocephalic vessel blood flow indices in patients of both groups using pulse doplergraphy. The use of Natrium Nitroprussidum used buccaly in patients with cerebral-ischemic form of arterial hypertention and hyportensive disease differentiates in terms of indices characterising the formation, transport and utilisation of energetic products, products of POL and antioxidant ferments.