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.

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.

Role of MAPK ERK1/2 and p38 in the Regulation of Secretory Functions of Different Populations of Neuroglia in Ethanol-Induced Neurodegeneration.

We studied the participation of ERK1/2 and p38 in secretion of neurotrophic growth factors by various types of neuroglia under conditions of in vitro and in vivo modeled ethanol-induced neurodegeneration. The inhibitory role of these protein kinases in the production of neurotrophins by intact astrocytes and the absence of their participation in the regulation of functions of oligodendrocytes and microglial cells were shown. Under conditions of ethanol neurotoxicity, the role of ERK1/2 and p38 in the production of growth factors by glial elements was significantly changed. Neurodegeneration modeled in vitro led to inversion of the role of both protein kinases in the secretion of neurotrophins by astroglia and inhibition of the cytokine-synthesizing function of oligodendrocytes and microglial cells by ERK1/2 and p38. In mice receiving ethanol per os for a long time (as well as in cells in vitro exposed to ethanol), mitogen-activated kinases stimulated the function of astrocytes and inhibited the production of growth factors by microglial cells. At the same time, chronic alcoholization was accompanied by the appearance of the stimulating role of ERK1/2 and p38 in the implementation of the secretory function by oligodendrocytes.

Effectiveness of Phenolic Antioxidants in Experimental Model of Benign Prostatic Hyperplasia.

Experimental model of sulpiride-provoked benign prostatic hyperplasia was employed to comparatively assess the effect of phenolic antioxidants (dihydroquercetin, p-thyrozol, dibornol, and prostagenin) on prostate morphology. All examined agents decreased the degree of hyperplasia in acinar epithelium; the greatest efficacy was demonstrated by prostagenin. Moreover, dihydroquercetin and p-thyrozol increased the cross-section area of acinar lumina and prostate volume, which is inadmissible in this pathology. These results suggest that the use of phenolic antioxidants in the therapy of benign prostatic hyperplasia should be strictly controlled.

Dihydroquercetin Improves Microvascularization and Microcirculation in the Brain Cortex of SHR Rats during the Development of Arterial Hypertension.

The effects of dihydroquercetin (50 mg/kg intragastrically daily for 6 weeks) on the density of capillary network (mean number of capillaries per mm2), mean capillary diameter, structure of capillary network, capillary diameter distribution (<3, 3-5, 5-7, and 7-9 µ), and local cerebral blood flow (by laser Doppler) in the visual cortex were studied in SHR rats during the development of arterial hypertension (from the 6th to the 12th week of life). Normally, the systolic and diastolic BP progressively increased in SHR rats during this period. Dihydroquercetin did not affect the development of arterial hypertension. At the same time, the drug significantly increased the mean diameter of capillaries (by 11%), capillary network density (by 23%), and in the percentage of capillaries with a diameter of 3-9 µ (passable for erythrocytes; by 42%). Positive effects of dihydroquercetin on the structure of microcirculatory bed improved microcirculation: local cerebral blood flow in the visual cortex of SHR rats was significantly higher (by 36%) than in rats receiving no flavonoid and close to the value in Wistar-Kyoto rats. Dihydroquercetin improved microvascularization and microcirculation in the cerebral cortex of SHR rats during the formation of arterial hypertension.

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.

Quantitative Evaluation of Primordial Follicles in Rat Ovaries during the Early and Delayed Terms after Different Cytostatic Exposures.

Experiments on female Wistar rats showed that cytostatic agents (farmorubicin, platidiam, carboplatin, and etoposide) induce an initial significant decrease in the number of primordial follicles. Over the next 2-3 estrous cycles after administration of farmorubicin, platidiam, and carboplatin, this index practically did not differ from the control. The number of primordial follicles in the third and fourth estrous cycles after farmorubicin administration, as well as in the second and sixth estrous cycles after etoposide administration was much higher than the follicular reserve after cytostatic treatment (first estrous cycle). The ovarian reserve was exhausted in the delayed period after the start of the experiment. This dynamics of the pool of primordial follicles suggests that the ovary of rats in the postnatal period of life contains a limited number of female germline stem cells.

Experimental Simulation of Traumatic Osteomyelitis in Rats.

A model of traumatic osteomyelitis in rats is created. The disease development was evaluated by bone marrow myelograms, results of scintigraphy, and histological studies.

[PARAMETERS OF CEREBRAL CORTEX CAPILLARY NETWORK IN SHR RATS DURING THE DEVELOPMENT OF ARTERIAL HYPERTENSION AND STABLE HIGH BLOOD PRESSURE].

The studies were performed in hypertensive rats (SHR strain) during the period of hypertension development (7-8 weeks) and stable high blood pressure (16-17 weeks) and in normotensive rats (WKY strain) of corresponding ages. The average number of capillaries per square millimeter, the average capillaries diameter, and the capillary network structure following the estimation of capillaries distribution based on capillaries diameter within the following ranges (up to 3, from 3 to 5, from 5 to 7 and from 7 to 9 µm) were investigated using the morphological approach. The average diameter of capillaries and capillary network structure in SHRs during the development of hypertension did not differ from the respective values in WKY rats of the same age. SHR rats showed disturbed microvascularisation by structural and functional rarefaction in the stable high blood pressure period, which was manifested in lower average capillaries density and average capillaries diameter as well as in substantial (2.5 times) increase in plasmatic capillaries as compared to WKY rats of the same age.

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.

Dihydroquercetin effects on the morphology and antioxidant/prooxidant balance of the prostate in rats with sulpiride-induced benign hyperplasia.

A course of dihydroquercetin (antioxidant) injections to 5-month-old Wistar rats with sulpiride-induced benign prostatic hyperplasia led to reduction of proliferative activity in the glandular structures and to attenuation of the inflammatory reaction in the tissue. Prostatic antioxidant/prooxidant balance returned to normal after the treatment.

Simulation of category IIIB prostatitis.

Blood flow arrest in the inferior vena cava at the level of the inferior pole of the kidney led to the development of epithelial degeneration and stromal sclerosis after 1.5 months, dilatation of the veins, and congestion of secretion in rats. These signs corresponded to the morphological picture of category IIIB prostatitis or to signs of noninflammatory chronic prostatitis (hemodynamic disorders, sclerosis, degeneration). On the other hand, there was no cellular infiltration of the glandular tissue associated with infection and inflammation.

Role of receptors to fibroblast growth factor (FGF) on mesenchymal precursor cells in the realization of regenerative effects of alkaloid songorine.

We studied the mechanisms of regenerative (wound healing) effects of songorine associated with functional activation of mesenchymal progenitor cells. The key role of FGF receptors on these progenitor cells in the stimulation of realization of their growth potential under the effect of the alkaloid was demonstrated. Under in vitro conditions, the antibodies to FGF receptor abolished the songorine-induced increase in the number of fibroblast colony-forming units in bone marrow cell culture. The intensity of differentiation of mesenchymal precursors remained unchanged.

Comparative evaluation of the efficiency of prostatotropic agents of natural origin in experimental benign prostatic hyperplasia.

Comparative evaluation of the efficiency of prostatotropic agents was carried out in rat experiments. Serenoa repens plant preparation and polypeptides isolated from the cattle prostate were used for the treatment of benign hyperplasia. Drugs in parallel with sulpiride similarly led to shrinkage of the acinar epithelial area and to emergence of a trend to an increase of the stromal/epithelial proportion, more so after Serenoa repens treatment.

Mechanisms of regeneratory effects of baikal aconite diterpene alkaloids.

Regeneratory activities of Baikal aconite alkaloids were studied on the excision skin wound model. Manifest wound healing effects of songorine, napelline, and hypaconitine were detected. The therapeutic efficiency was based on activation of residual mesenchymal progenitor elements. The development of this phenomenon was explained by the direct effects of alkaloids on precursors and by higher production of growth factors by the skin stromal cells. Songorine exhibited the most pronounced specific activity due to more significant stimulation of progenitor cell differentiation associated with maximum activation of the secretory function of the microenvironment cells.

Tissue reaction to a titanium-nickelide mesh implant after plasty of postresection defects of anatomic structures of the chest.

We studied morphological features of the regenerate formed after postresection defect plasty of the pericardium, diaphragm, and thorax with a mesh implant made of nanostructural titanium-nickelide threads. The newly formed tissue grew through the implant with the formation of an integrated tissue regenerate ensuring anatomic and physiological restoration of this area.

Hepatoprotective effects of immobilized granulocyte colony-stimulating factor and hyaluronidase preparation and their mechanisms.

High hepatoprotective activity of granulocytic CSF and hyaluronidase immobilized using electron-beam immobilization technology was demonstrated on the model of CCl(4)-induced hepatitis: the preparations produced anticholestatic, anti-inflammatory, and antisclerotic effects. These effects developed against the background of stimulation of bone marrow multipotent precursor cells and their mobilization into circulation accompanied by an increase in the content of parenchymatous progenitor cells in the liver. The most pronounced positive effect was observed in combined treatment with the test preparations.

Pharmacology of somatrotropin pegylated by electron-beam synthesis nanotechnology.

Pharmacological characteristics of somatotropin pegylated using electron-beam synthesis nanotechnology (PEG-STH) were studied. Oral PEG-STH stimulated the intensity of protein and lipid metabolism and endochondral bone growth without modifying the processes of periosteal and endosteal bone formation. Specific activity of this substance administered orally significantly surpassed that of parenteral non-modified growth hormone.

Experimental study of the efficiency of impaza on the model of chronic aseptic prostatic inflammation.

We compared the efficacy of Impaza (antibodies against endothelial NO-synthase in ultra-low doses) and Serenoa repens on the rat model of chronic aseptic prostatic inflammation. Administration of Serenoa repens in a dose of 50 mg/kg for 1.5 months prevented the development of prostate sclerosis and increased luminal area, but did delay the development of atrophic processes. In animals treated with Impaza (3 ml/kg for 1.5 months), atrophic changes in the prostate gland were practically absent. These findings indicate that Impaza can be used in complex therapy of abacterial prostatitis.

Antioxidant composition causes antiexsudorific effect in the model of chronic venous insufficiency.

Venous hypertension and swelling of the hind limbs was demonstrated to develop in rat model of chronic venous insufficiency. It was found that 14-day course of dihydroquercetin (50 mg/kg) and lipoic acid (50 mg/kg) administered intragastrically prevented the increase in hind limb volume and reduced the severity of edema of rat muscle tissue in chronic venous insufficiency.