Changes in the Biorhythms of Biochemical Parameters in Animals with Modeled Acute Desynchronosis.

This article describes models for the study of acute desynchronosis: jetlag syndrome and acute desynchronosis under physical stress for possible pharmacological correction of these disorders. The cosinor analysis allowed assessing significance of changes in biological rhythms in 2 biological models: the jetlag-type diurnal rhythm shift model and the model with changed light mode. The revealed changes in the rhythms of biochemical parameters in the blood serum of animals with acute desynchronosis indicate significant changes in the intensity of carbohydrate-lipid metabolism, which affected the processes of cell bioenergetics. These changes are most pronounced in the group of animals that were kept under conditions of constant darkness, which can serve as a marker of the initial stage of pathological desynchronosis. The jetlag-type model can be used to evaluate the effectiveness of the pharmacological correction of physiological desynchronosis. The model with modified light regimen can be used for evaluation of the effectiveness of pharmacological correction of pathological desynchronosis.

Polymorphism of Oprm1 Gene and Its Association with Manifestations of N-(1-Phenethyl-4-Piperidyl)Propionanilide Intoxication in Rats.

We studied association of Oprm1 gene polymorphisms with signs of N-(1-phenethyl-4-piperidyl)propionanilide intoxication in rats. It was found that the rate of intoxication in laboratory animals depends on genetic features. A polymorphic variant rs105312806 of Oprm1 gene can be a possible marker of animal sensitivity to opioid receptor agonists. This hypothesis was supported by differences in the rats of intoxication signs such as time to lateral posture and sleep duration in homozygous rats carrying different alleles. In rats with AA genotype, the time to lateral posture was shorter by 1.3 times and sleep duration was longer by 3.5 times than in carriers of GG genotype.

[Clinical and experimental study of the peculiarities of cardiac activity disorders during poisoning by combustion products in persons of different age groups.]

The work is carried out to clarify the mechanisms of cardiac activity disorders and assess the severity of cardiotoxicity in acute poisoning by combustion products in the age aspect. 71 patients with severe carbon monoxide poisoning were examined. The comparison group consisted of 22 patients with acute severe opiate poisoning. The methodological basis of the clinical study was daily monitoring of ECG. The studies were performed in 1 and 3-4 days. Residual cardiac dysfunction was estimated at 12-14 days. The comparison group selected 14 patients with acute myocardial infarction at this stage. Pathomorphological changes were studied on the cadaveric material of 24 experimental animals exposed to carbon monoxide at a dose of 16 g/m3 for 5 minutes on 31 days from toxic injury. It is established that acute poisoning by combustion products leads to the development of severe electrophysiological disorders classifying cardiotoxic effect as severe or extremely severe. Expression of signs of cardiotoxicity is higher in middle-aged and elderly patients. In the outcome of the poisoning, all the victims have formed a toxic cardiomyopathy.

Influence of Implants Surface Properties on Bone Tissue Formation in the Ectopic Osteogenesis Test.

We studied the influence of the characteristics of oxide porous coatings on osteogenesis and integration of new bone tissue and titanium implant surface in the ectopic osteogenesis test. Implants with coating with pore size 2-20 µ exhibit better osteogenic and osteoconductive characteristics than implants with homogenous surface and smooth relief (pore size 0.5-5.0 µ). Physical characteristics of the surface of the material along with chemical composition of the coating are essential for the formation of bone tissue and its integration with the implant.

Assessment of Expression of Genes Coding GABAA Receptors during Chronic and Acute Intoxication of Laboratory Rats with Ethanol.

Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3.

[Concomitant impact of organic pathology on the development of cognitive impairment in patients with attack-like paranoid schizophrenia].

The study included 47 patients (23 men, 24 women) with ICD-10 diagnosis of attack-like paranoid schizophrenia. Patients were divided into two groups: with- (25 patients) or without (22 patients) a concomitant organic disease. Memory, attention and thinking were assessed with psychometric tests. Inter- and intra-group differences were identified that indicated a considerable impact of a concomitant CNS organic pathology on the development of cognitive impairment in the schizophrenic process and active antipsychotic therapy. The data obtained can be used in the development of a differentiated approach to the treatment of patients with concomitant organic pathology.

[Cytogenetic examination of the workers of higher chemical hazard enterprises and the population of the nearby territories].

Cytogenetical examination was made in 49 workers of higher chemical hazard enterprises and 26 dwellers from industrial communities, who were engaged in enterprise security. Analysis of chromosome aberrations (CA) in the examined groups revealed a 1.8-fold increase in total CA rates in the industrial community dwellers securing the enterprise as compared to the controls mainly due to the rise in the rate of single fragments. At the same time in the enterprise workers, the total level of CA was 2.36- and 4.1-fold greater than that in the population of industrial communities and in the controls, respectively; and it was also characterized by a broad spectrum of CA with the increased number of both chromatid and chromosomal exchange aberrations.

Experimental study of cytoprotective effect of melatonin in radiation exposure.

The effects of a synthetic analog of melatonin in doses of 10 and 50 mg/kg on the incidence of chromosome aberrations in bone marrow cells was studied in outbred rats exposed to single short-term γ-irradiation in doses of 2 and 4 Gy. Melatonin injected 30 min before the exposure 2-fold reduced the incidence of chromosome aberrations. Possible mechanisms of anticlastogenic effect of melatonin are discussed.

[Adaptive immune response of people living near chemically hazardous object].

The article presents data dynamics of adaptive immune responses of people for a long time living in adverse environmental conditions caused by pollution of the environment by industrial toxic waste. It is shown that in the process of adaptation to adverse environmental factors, changes in the immune system are in the phase fluctuations of immunological parameters that are accompanied by changes in the structure of immunodependent pathology. Most sensitive to prolonged exposure to toxic compounds are the cellular mechanisms of immune protection. Violations of the structural and quantitative and functional parameters of the link of the immune system are leading to the formation of immunopathological processes.

[Substantiation of possibility of use GABA-receptor's chloride channel blockers for modelling of the temporal epilepsy].

In work the review of some clinik-morphological and pharmacological researches devoted to a temporal epilepsy and its experimental models is resulted. On the basis of the analysis of existing problems in working out antiepileptic drugs and in studying of mechanisms epilepsy necessity of development of new chronic experimental models of a temporal epilepsy is proved. The basic criteria of experimental model of a temporal epilepsy are generalised. It is shown that parametres of acute toxicity and the remote consequences of an intoxication convulsive agents from group GABA-receptor's chloride channel blockers correspond to the basic criteria a post-epistatus of model of a temporal epilepsy. The conclusion is presented on use possibility GABA-receptor's chloride channel blockers in quality agents for modelling of a temporal epilepsy.

Evaluation of the neurological status in experimental acute alcohol intoxication.

Approaches to evaluation of the severity of neurological disorders in animals with experimental acute severe alcohol intoxication were developed. Using the method of statistical analysis, we selected criteria, which can be used for evaluation of the severity of inhibition of the nervous system in studies of the alcoholism pathogenesis and for improvement of methods for correction of severe intoxication at the preclinical stage of drug efficiency evaluation.

Relationship between osteoinductive characteristics of biocomposite material and physicochemical characteristics of coating.

The osteoinductive characteristics of hydroxylapatite-based coating with different physicochemical characteristics were studied. The formation of the bone tissue on the studied types of the implant coating differed by the pattern and rate of formation of structural elements of the bone. Clear-cut phase-wise osteogenesis was seen on combined calcium phosphate coating: intense formation of the fibrous interstitial substance (due to cellular structure of hydroxylapatite) and slow maturing of cell elements. Bilayer composite coating provided (during the same period) the formation of more mature connective tissue. This phenomenon can be explained by better bioavailability of the coating material. The properties of combined calcium phosphate coating can be evaluated as mainly osteoconductive, while those of bilayer composite coating as osteoinductive.

Osteogenic potential of mesenchymal stem cells from bone marrow in situ: role of physicochemical properties of artificial surfaces.

Correlation analysis demonstrated the role of inorganic parameters of the surfaces of calcium phosphate materials in the regulation of osteogenic differentiation of mesenchymal precursors. The progenitor stromal cells were isolated from syngeneic bone marrow immobilized in vitro on calcium phosphate surfaces with different structure, phasic, and elemental composition. After 45 days of subcutaneous ectopic osteogenesis in BALB/c mice, the tissues grown on these matrixes were characterized histologically. It was found that adhesion of bone marrow cells is the initial stage determining their future proliferation (conduction) over the artificial surface and the area of formed tissue plate. The success of histogenesis depends on surface roughness. The optimal roughness class was 4-5 (Russian State Standards), which enables differentiation of progenitor stromal cells under the specific microenvironmental conditions into the connective and adipose tissue cells. Differentiation of the progenitor cells into the stromal cells producing the hemopoiesis-inducing microenvironment also takes place in the foci of active hemopoiesis. Induction of osteogenic potential of the stromal precursors (osteoinduction) is determined by the ratio between calcium and phosphate atoms in surface coatings. In our experimental system, osteogenic differentiation of stromal mechanocytes was blocked only at Ca/P<0.5.

[The effect of perftoran on the resistance of mice to GABA receptor antagonists and on the antidote activity of anticonvulsant agents]. / Vliianie perftorana na ustoichivost' myshei k antagonistam GAMK-retseptorov i antidotnuiu aktivnost' protivosudorozhnykh sredstv.

Perfluorane (a phenobarbital-type inducer of the microsomal enzyme system) raised the resistance of mice to the toxic effect of picrotoxin and bicucullin in 7 days after injection. The antidote effect of diazepam and phenobarbital increased under such conditions. In experiments in vitro a modulatory effect of perftorane on the central muscarine and benzodiazepine receptors was demonstrated.