The condition was studied of the brain monooxigenase system (MOS) in experimental subarachnoidal hemorrhage in rats. The results show that the above hemorrhage leads to a significant depression of activity of brain MOS enzymes (cytochrome P-450, NADPN-cytochrome C-reductase). Depression of activity of the enzymic system is manifest from day 1 and has a tendency toward reduction but at day 14 and 21 the indices are still below the control values. Under the exposure to phenobarbital the reduction of activity of the enzyme system in subarachnoidal hemorrhage gets accelerated, with normalization of the indices occurring by day 7 after the hemorrhage.

The level of expression of oxyR, the gene that protects Escherichia coli against oxidative stress, was enhanced by physiological concentrations of the biogenic amine putrescine. This level was directly proportional to the degree of negative DNA supercoiling. 1,4-Diamino-2-butanone (DAB), a specific inhibitor of ornithine decarboxylase, the key enzyme of polyamine synthesis, produced an inhibitory effect on the level of oxyR expression under oxidative stress, which was relieved by the addition of putrescine. The direct relationship between putrescine concentration and the degree of negative DNA supercoiling suggests that the mechanism of action of putrescine as the modulator of oxyR transcription activity is based on both its direct influence on the gene expression level and its indirect effect mediated by topological DNA changes. Putrescine was shown to produce a protective effect if the DNA is damaged by reactive oxygen species.

The effect of the ACTH(4-10) analog Semax on immediate early gene c-Fos expression was studied in Wistar rats with high and low resistance to emotional stress under the usual conditions and during psychoemotional loading. Fos-immunoreactive cells in the were counted automatically with the help of a computer. It was shown that under the usual conditions the intraperitoneal Semax injection induced immediate early gene c-Fos expression in the lateral septal region in rats predisposed to emotional stress and in the paraventricular hypothalamus in rats of both groups. Preliminary Semax injection decreased the stress-induced c-Fos expression in the paraventricular hypothalamus and medial septum in rats predisposed to emotional stress and tended to reduce the number of stress-induced c-Fos-immunopositive cells in the lateral septum and basolateral amygdala in both groups of animals. The obtained data suggest that Semax differently affects the immediate early c-Fos gene expression in the brain of rats resistant and predisposed to emotional stress and this effect reflects the antistressor properties of the regulatory peptide.

Experiments on the Wistar rats showed that neonatal daily injections of phenobarbital (35 mg/kg) during first 3 days of life resulted in the enzyme imprinting of liver microsomal monooxygenases. Rise in the activities of liver microsomal oxidation enzymes is constantly maintained during all the life leading to increase in average lifespan of rats. Analysis of the survival curves in Gompertz equation co-ordinates showed that enzyme imprinting by phenobarbital caused changes in mortality patterns at different stages of ontogenesis. The phenomenon of enzyme imprinting by phenobarbital and lifespan prolongation was registered only in females but not in males. An inverse correlation was found between the duration of phenobarbital sleeping time and lifespan of rats.

The structural bases of cooperative effect of glucocorticoids and HDL brings about the activation of protein biosynthesis in hepatocytes. Using surviving rat liver it was shown that these two compounds together activate the gene expression which was indicated by increased 3H-uridine incorporation into the total RNA pool. The enhanced incorporation of 14C-leucine into proteins in these experiments confirms protein biosynthesis acceleration. With the use of liver perfusion technique it was morphologically demonstrated that the earliest changes in hepatocyte genome take place in nucleoli. The increase of nucleolar dimensions and granular component reflects the activation of ribosomal precursors synthesis. Considerable number of ribosomes in the hepatocyte perinuclear space indicates their active transport across the numerous nuclear membrane pores into the cytoplasm. In the first place and more prominently in hepatocytes the protein synthesis "for export" is stimulated, which was proved by the dynamics of ribosome accumulation on the membranes of endoplasmic reticulum according the perfusion duration. The kupffer cells play a significant role in HDL transcytosis and in the realization of their cooperative effect with glucocorticoids.

The heart is often refereed to as an "beta-adrenergic organ" because beta-adrenergic agonists are powerful stimulants of cardiac contractility. Catecholamines acting through beta-adrenoceptors produce both positive inotropic and chronotropic effects in human heart. It is now generally accepted that in human heart both beta 1- and beta 2-adrenoceptors coexist. beta-Adrenergic transduction system consist of membrane-bound beta-receptors, the effector enzyme adenylyl cyclase and guanine nucleotide-binding transduction (G) proteins. Repeated long-lasting agonist stimulus evokes homologous or heterologous desensitization of transduction system. Chronic heart failure accompanies with decreased responsiveness to beta-adrenoceptor agonists and is thought to exacerbate the loss of cardiac contractility. Depending on the etiology of heart failure abnormalities of the beta-receptor-G protein-adenylyl cyclase system result from a reduced of beta 1-receptors, uncoupling of beta 1- or beta 2-receptors, alteration of G-protein function, or decreased catalytic subunit activity of adenylyl cyclase and enhanced expression of beta-adrenoceptor kinase. The model most widely used is that of circulating lymphocytes that contain a homogeneous population of beta 2-adrenoceptors. The biochemical and pharmacological properties of human lymphocyte beta 2-adrenoceptors are quite comparable to those of heart beta 2-receptors. The analysis of lymphocyte beta 2-adrenoceptor-adenylyl cyclase system can be used as a model for long-term regulation of human cardiac beta 1- and beta 2-adrenoceptors only if serial changes in response to administration of non-selective beta-adrenergic agonists or antagonists are being investigated. This review concentrates on beta-adrenoceptors in human healthy heart and in heart failure and also on lymphocyte beta 2-adrenoceptors and on the changes of these receptors properties under the influence of some cardiotropic drugs.

Cytotoxicity genetic mechanisms such as induction of SOS-repair, excision repair and interstrand coupling induced by cycloplatam or ammine (cyclopentyl amine)-S(-) malatoplatinum (II), a new antitumor drug, were for the first time studied in comparison to those of the known drug cis-diammine dichloroplatinum (II) (DDP) in a model system of Escherichia coli. In the cells of E. coli the cycloplatam cytotoxicity was much lower than that of DDP. Both the drugs induced SOS-repair in E. coli PQ37. In a concentration of 25 microM DDP was 20 times as active as cycloplatam. In concentrations of 40 to 100 microM the difference leveled. Both the drugs induced interstrand coupling in specimens of pure DNA from calf thymus and E. coli. When the cells of the wild type E. coli AB1157 were incubated in the presence of the drugs only DDP induced the DNA interstrand coupling. No correlation between the DNA interstrand coupling induced by cycloplatam or DDP and cytotoxicity of the drugs was observed.

The expression of genes belonging to the Ada regulon of Escherichia coli under the action of mono- and bifunctional alkylating agents--high-efficiency antitumor HMM, ACNU, and BCNU preparations--was studied. The functional specificity of the alkA, alkB, and aidB1 genes concerning both the structure and volume of DNA alkylation and the specificity of cell preadaptation was revealed. Additional experimental evidence for the role of the aidB1 gene as a unique "hazard gene", a component of the E. coli ada operon, was obtained. A phenomenon of positive interference between alternative SOS and Ada responses was observed for the first time upon gene expression.

Analysis of cytostatic therapy effects on expression of gene MDR-1 in hemopoietic cells of patients with acute leukemia (AL) in complete clinicohematological remission (CCHR).

Data about enzymes involved in metabolism and detoxification of xenobiotics in fish are summarized. Special attention is given to the comparison of monooxygenase systems of fish and mammals. 3-Methylcholanthrone, benzo-pyrene, benzo-naphthoflavone, and various technogenic pollutants present in water are examined as inducers of fish monooxygenase systems. The induction of cytochrome P-450 isozymes is specially reviewed, and we discuss their difference from similar isozymes of other vertebrates classes. We also discuss the relationship between the activity of the monooxygenase system in fish and temperature conditions of water bodies, as well as sex-related differences in the activity of this system. Perspective in the use of the monooxygenase system for biological monitoring are reviewed.

Small alpha-RNP of K-562 cells contain a small RNA as an RNA component, this RNA is homologous to Alu-repeating sequences of human DNA. When cells are exposed to dimethylsulfoxide, an agent inducing cell differentiation along the erythroid pathway, the content of both high-molecular-weight (heterogeneous nuclear and messenger) RNA enriched with Alu repeats and low-molecular-weight specific RNA, small Alu-homologous alpha-RNA undergoes a coordinated decrease. Using the technique of northern blot hybridization, we have demonstrated nonuniform distribution of Alu repeats both in the fraction of total low-molecular-weight RNA of the cytoplasm as well as in the fraction of messenger RNA. It is proposed that alpha-RNA (alpha-RNP) participates in the control of expression of non-linked Alu-containing genes.