Effect of a helium and oxygen mixture on physiological parameters of rats with cerebral arterial air embolism.

Introduction: Cerebral arterial air embolism (CAE) is a serious and potentially dangerous condition that can interrupt the blood supply to the brain and cause stroke. One of the promising gas mixtures for emergency treatment of air embolism is an oxygen-helium mixture. Methods: We modeled CAE in awake rats by injecting air into the common carotid artery. Immediately after CAE, animals were either untreated or underwent hyperbaria, oxygen inhalation, heated air inhalation, or helium-oxygen mixture inhalation. Body temperature, locomotor activity, respiratory and cardiovascular parameters were monitored in the animals before CAE modeling, and 3 and 24 h after CAE modeling. Results: After 3 hours of CAE modeling in awake rats, depression of the nervous, cardiovascular and respiratory systems, as well as decreased body temperature were observed. 24 h after CAE modeling multifocal cerebral ischemia was observed. Normobaric helium-oxygen mixture inhalation, on par with hyperbaric treatment, restored body temperature, locomotor activity, respiratory volume, respiratory rate, and blood pressure 3 hours after CAE, and prevented the formation of ischemic brain damage lesions 24 h after CAE. Discussion: Thus, inhalation of a heated oxygen-helium gas mixture (O2 30% and He 70%) immediately after CAE improves the physiological condition of the animals and prevents the foci of ischemic brain damage formation.

Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS.

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

Effect of Standard and High-Fat Diets during Modeling of Streptozotocin-Induced Diabetes in Rats on the Development of Complications.

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

Mouse Model for Assessing the Subchronic Toxicity of Organophosphate Pesticides.

The development of antidotes to organophosphate poisons is an important aspect of modern pharmacology. Recombinant acetylcholinesterase and butyrylcholinesterase are effective DNA-encoded acceptors of organophosphate poisons and, in particular, pesticides. Here, we present the results of a study on the effectiveness of recombinant butyrylcholinesterase (BChE) in modeling organophosphate poisoning caused by oral administration of paraoxon at a dose of 2 mg / kg. The study showed a high activity of BChE as a protective agent for subchronic anticholinesterase poisoning in an in vivo model. The administration of BChE in a dose of 20 mg / kg allows one to avoid mortality, and also contributed to rapid recovery after model poisoning.

[Lymphocyte subpopulations, levels of interferon, and expression of their receptors in patients with chronic hepatitis B and C: Correlation with the species of viruses and the degree of liver fibrosis]. / Subpopuliatsii limfotsitov, uroven' interferonov i ékspressiia ikh retseptorov u bol'nykh khronicheskimi gepatitami V i S: zavisimost' ot vida virusov i stepeni fibroza pecheni.

AIM: To determine whether there is a correlation of the composition of circulating lymphocyte subpopulations, the serum concentrations of interferon (IFN)-α, IFN-γ, and IFN-λ3, and the lymphocyte expression of types I and II IFN receptors with the species of a disease pathogen and the degree of liver fibrosis (LF) in patients with chronic hepatitis B (CHB) and in those with chronic hepatitis C (CHC). SUBJECTS AND METHODS: The investigation enrolled 44 patients with CHC, 9 patients with CHB, and 13 clinically healthy donors. The degree of LF in the patients was determined using transient elastography. The composition of peripheral blood lymphocyte subpopulations was examined; the concentrations of IFN-α, IFN-γ, and IL-28B were estimated. RESULTS: Lymphocyte counts were higher in patients with CHC and in those with CHB than those in healthy donors; and the number of neutrophils was lower. There were no differences between the groups in the composition of lymphocyte subpopulations with the exception of the number of CD3+CD4+ cells, which in patients with CHC was larger than in those with CHB. In CHC and CHB patients, the counts of CD118+ lymphocytes were higher than those in healthy donors. Patients with CHB and those with CHC did not differ between themselves and from healthy donors in the expression of CD119 on the lymphocytes. In CHC patients, the relative CD119+ cell counts were higher between CD4+ lymphocytes than those in healthy donors. The serum levels of IFN-α and IFN-γ in CHC and CHB patients were similar, but higher in healthy donors. The concentration of IL-28B genotype in patients with CHC was twice as high as in those with CHB, but the differences were statistically insignificant. The number of lymphocytes increased with the progression of fibrosis; that of neutrophils decreased. There was an inverse relationship between platelet counts and LF severity. Multiple comparisons of the clusters of patients with different degrees of LF revealed no differences in the number of major lymphocyte subpopulations. However, the number of CD3+CD16+CD56+ natural killer-like T (NKT) cells correlated with fibrosis severity. Patients with different degrees of LF showed no differences in the proportion of CD118- and CD119 cells between lymphocytes and in the serum levels of IFN-α, IFN-γ, and IL-28B levels. Patients with grade IV LF displayed a higher proportion of CD4+CD119+ lymphocytes between CD45+ cells than did those with grade III LF. CONCLUSION: Several new clinical and laboratory trends were identified and the nature and extent of previously described hematological and immunological changes were clarified in CHC or CHB patients with various degrees of LF. Some indicators may be used as additional criteria for the prognosis of the above forms of hepatitis, and a number of newly described facts suggest that it is necessary to revise the protective/phlogogenic value of types I, II, and III IFNs in chronic viral hepatitis C and B.

[The indicators of immune status of peripheral blood of donors].

The expanded analysis of 57 samples of peripheral blood from conditionally healthy patients was implemented concerning phenotype of main populations of lymphocytes, activated pools of cells and level of cytokines. The samples were received in the department of storage of blood and its components of the research institute of blood transfusion of the hematology research center. It is demonstrated that number of T-lymphocytes, T-helpers and activated TY-cells with phenotype CD3+HLA-R+ and level of detected cytokines by standard indicators had no difference with publications data. In particular cases an increase of number of cytolytic T-lymphocytes, B-lymphocytes and natural killers and decrease or increase of CD4/CD8 index relative to standard were detected. The decrease of number of natural killers was the most frequent aberration. The study demonstrates that among conditionally healthy patients giving blood as donors persons with disorders of immune system were presented.

Improvement of cardiac contractile function in rats with postinfarction cardiosclerosis after transplantation of mononuclear and multipotent stroma bone marrow cells.

We compared the efficiency of autologous mononuclear cells and multipotent stromal cells of the bone marrow after their non-selective intracoronary transplantation on day 30 after acute coronary infarction in rats. Improvement of hemodynamic parameters of myocardial contractility (rates of left ventricular pressure rise and drop) in comparison with the initial values and deceleration of postinfarction prolongation of QRS and QT intervals were observed in rats of the experimental group in contrast to controls in 4 weeks after transplantation. These functional changes were more intensive after transplantation of multipotent stromal cells and were accompanied by more pronounced morphological signs of reverse myocardial remodeling: thickening of the scarred left ventricular wall, shrinkage of the scar, and decrease in left ventricular dilatation index.

Directions of migration of bone marrow mononuclears after intracoronary transventricular injection.

Directions of migration of mononuclear bone marrow cells after intracoronary transventricular injection procedure developed by us were experimentally studied. After nonselective injection of cells into the right and left coronary arteries in rats, the labeled cells were detected only in the damaged zone of the myocardium. Localization of transplanted mononuclears in the scar attests to their homing into the damaged zone. Numerous cells were found in the red pulp of the spleen and solitary cells were detected in the liver and lungs. In the heart, the labeled transplanted cells were detected only in the scar zone at all terms of the study; they were not incorporated into the vascular walls, but were surrounded by thick bundles of collagen fibers and probably underwent differentiation into fibroblasts. No data on possible differentiation of the transplanted cells into vascular cells or cardiomyocytes were obtained.

[Somatic maturation and sensorimotor development of C57BL/6 mice prenatally exposed to cytosine arabinoside].

The topical problem of experimental neurobiology is the development of pharmacological models to search for correlation between induced brain pathology and changes in behavioral phenotype. Cytosine arabinoside (Ara-c) is an antiproliferative agent, exposure to which in the critical period of the embryonic formation of the cortex results in the abnormality of its development. This study was aimed at estimation of the somatic and sensorimotor aspects of the early postnatal maturatrion of behavioral acts in mice with developmental abnormalities of the cortex induced by Ara-c. Pregnant C57BL/6 mice were injected with the substance on the 12.5th 13.5th gestation days. Offspring behavior was studied using a modified Fox battery on the 1st-21st postnatal days. Severe disorders of the sensorimotor development with slight somatic changes were revealed in the offsprings of Ara-c-treated mice. Features of these pathological changes point to a correlation between the developmental changes in behavioral phenotype and irregularities of the cortex formation. This experimental model can be applied to neurobiological and pharmacological studies.

Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats.

Changes in blood pressure and sympathetic nerve activity induced by local injection of endothelin-1 into the rostroventrolateral medulla were studied in narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a transient increase in blood pressure and sympathetic nerve activity followed by progressive hypotension and bradycardia. Pretreatment with ETB-receptor antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1 abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor blockade was most effective in normotensive rats. Our findings suggest that cardiovascular disorders in SHRSP rats can be related to peculiarities in the rostroventrolateral medullar endothelin system.

[Effect of moxonidine on the cardiac chronotropic regulation in hypertensive rats SHR-SP]. / Vliianie moksonidina na kardiokhronotropnye mekhanizmy reguliatsii u gipertenzivnykh krys SHR-SP.

The administration of moxonidine for two weeks in a daily dose of 2 or 10 mg/kg (p.o.) reduced the cardiac sympathetic tone in stroke-prone spontaneously hypertensive rats (SHR-SP) by 24.3 +/- 7.3 and 32.2 +/- 10.2%, respectively. In addition, the treatment influenced the cardiac baroreflex by decreasing the bradycardic plateau and increasing both bradycardic and tachycardic range. The baroreflex gain increased in a dose-dependent manner by 41.6 +/- 12.1 and 103.0 +/- 3.9%, respectively. These data indicate that moxonidine can modulate the cardiac autonomic (tonic and reflex) chronotropic control.

[Effect of daflon on the transcapillary fluid exchange in hindlimbs of anesthesized Wistar rats]. / Vliianie daflona na transkapilliarnyi obmen zhidkosti v zadnikh konechnostiakh narkotizirovannykh krys Vistar.

The effect of daflon administration (100 mg/kg/day, p.o., over 8 days) upon the transcapillary fluid shift in the hind extremities of narcotized rats was studied. The effect was evaluated by the arterio-venous difference of the blood density (orthostatic versus antiorthostatic). The treatment reduced the level of fluid filtration from the vascular channel to the interstitial space, but did not affect the level of reabsorption.

Role of I(1)-imidazoline receptors and alpha2-adrenoceptors in hemodynamic effects of moxonidine administration into the rostroventrolateral medulla.

Local injection of 4 nmol moxonidine (unilaterally) into the rostroventrolateral medulla of spontaneously hypertensive rats (SHR-SP) decreased mean blood pressure and heart rate by 24+/-3 and 3+/-4%, respectively. Pretreatment with the I1/alpha2-receptor antagonist efaroxan abolished the moxonidine-induced decrease in mean blood pressure, but had no effect on heart rate. Yohimbine blocked hypotension, delayed bradycardia (8 nmol), or completely inhibited the effects of moxonidine (16 nmol). Our results indicate that both I1-imidazoline receptors and alpha2-adrenoceptors of the rostroventrolateral medulla are involved in the realization of moxonidine-induced changes.

Role of the rostroventrolateral medulla in moxonidine-induced changes in cardiochronotropic regulation.

The cardiac component of baroreflex and sympathetic tone of the heart were studied in SHR-SP rats receiving moxonidine intragastrically or into the rostroventrolateral medulla. Moxonidine administered intragastrically in a dose of 10 mg/kg had no effect on cardiac sympathetic tone, but reduced the intracardiac rhythm and enhanced baroreflex bradycardia. Local injection of moxonidine into the rostroventrolateral medulla decreased cardiac sympathetic tone, but did not change the amplitude of baroreflex chronotropic responses. Our results indicate that changes in cardiochronotropic regulation after systemic administration of moxonidine are not mediated by the rostroventrolateral zone of the medulla oblongata.

[Participation of central and peripheral I1-imidazollinovykh and alpha2-adrenergic receptors in realizing the effects of moxonidine]. / Uchastie tsentral'nykh i perifericheskikh I(1)-imidazolinovykh i alpha2-adrenergicheskikh retseptorov v realizatsii éffektov moksonidina.

The role of the central and peripheral I1-imidazoline and alpha 2-adrenergic receptors in the development of hypotension and bradycardia induced by the intravenous injections of moxonidine was studied, in stroke-prone spontaneously hypertensive (SHR-SP) rats. The intravenous and local injections of I1--alpha 2 antagonist efaroxan (Efa) into the rostral ventrolateral medula (RVLM) abolished the moxonidine-induced fall of blood pressure, but did not eliminate bradycardia. The alpha 2 antagonist yohimbine (Yoh) injected into RVLM did not influence the moxonidine effects, whereas the intravenous Yoh injections fully blocked these effects. Thus the hypotensive action of moxonidine is mediated predominantly by the I1-imidazoline RVMM receptors, while the heart rate decrease is partly realized via the alpha 2 adrenoreceptors of peripheral innervation.

[Effects of chronic administration of moxonidine in hypertensive rats SHR-SP]. / Effekty khronicheskogo vvedeniia moksonidina u gipertenzivnykh krys SHR-SP.

Study of the hemodynamic response (arterial pressure and heart rate) by radio- and telemetric techniques in stroke-prone hypertensive rats (SHR-SP) aged 6-7 months showed that a chronic oral administration of moxonidine at a daily dose of 2 and 10 mg/kg) leads to hypotension (7 +/- 3 and 21 +/- 5%, respectively) and bradycardia (5 +/- 1 and 14 +/- 5%, respectively). The moxonidine administration at a greater dose violated the circadian heart rate profile, reduced the motor activity of rats by 34 +/- 15%, and showed a drug dependence syndrome in the heart rate (but not in the arterial pressure). It is concluded that moxonidine administration at large doses may give rise to side effects.

[Pharmacological analysis of the role of central alpha-2 adrenergic and imidazoline receptors in mechanism of the hypotensive effect of clonidine in rats]. / Farmakologicheskii analiz roli tsentral'nykh al'fa2-adrenergicheskikh i imidazolinovykh retseptorov v mekhanizme gipotenzivnogo deistviia klonidina u krys.

The role of alpha 2-adrenergic and imidazoline receptors in the hemodynamic response to clonidine (manifested by reduced arterial pressure, heart rate, and renal blood flow rate) was studied by injecting their antagonists with different affinity (yohimbine and idazoxan) into narcotized Sprague--Dawley rats. The local introduction (microinjection into rostral ventrolateral medulla) and systemic administration (intraperitoneal injection) of the drugs showed that the hemodynamic effect of clonidine is mediated predominantly by the central alpha 2-adrenergic receptors, rather than by the imidazoline receptors.

[Genetic aspects of arterial hypertension: the role of Y chromosome and mitochondrial DNA]. / Geneticheskie aspekty arterial'noi gipertensii: rol' Y-khromosomy i mitokhondrial'noi DNK.

A study on hybrids from reciprocal crossing of the SHR-SP and the WKY has shown that Y-chromosome and mitochondrial DNA the affect development of the spontaneous hypertension. The Y-chromosome takes part in disorders of baroreceptive sensitivity in phenylnephrine assay associated with hypertension. Although our findings suggest that structural remodelling of peripheral vascular resistance and an increase in noradrenaline-dependent vasocostriction is genetically determined in hypertensive rats, we could not corroborate the role of the Y-chromosome and mitochondrial DNA in the process. A difference was shown between male and female SHR-SP in the level of arterial pressure and in development of the vascular structure changes.

[Quantitative characteristics of the systemic anaphylaxis model in Sprague-Dawley rats]. / Kolichestvennaia kharakteristika modeli sistemnoi anafilaksii u krys linii Spreig-Douli.

Anaphylactic response intensity was quantitatively estimated by means of measuring mean arterial pressure (MAP) and heart rate (HR). Damage to intestinal mucosa was studied by means of morphometry. These indices grew in a dose-dependent way along with the amount of administered egg ovalbumin (OVA). The MAP and HR measurements seem to be useful in a quantitative elucidation of allergic sensitivity in laboratory animals.