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Participants of nuclear-powered submarine accident liquidation and special risk units' veterans participating in surface nuclear weapon tests as well as in liquidation of their consequences have been examined. It has been established that functional state of this category of people is difficult to interpret only in the context of radioactive irradiation effect or injuring stress factor exposure. This state is determined by a complex of psychotraumatic factors tending to become aggravated and characterizing by their individual significance and absolute or relative insolvability. In most representatives of this category the disease is manifested by psychopathologic syndrome of neurotic disorders (low spirits, emotional lability, asthenia, anxiety) and somatic disturbances as dysfunction of the cardiovascular, respiratory, digestive and other systems. The results obtained provide the pathogenetic substantiation of efficient ways and methods for rehabilitation of the special risk units' veterans. The data prove the necessity of appropriate correction of cardiovascular disorders in practically healthy servicemen residing under conditions of psychoemotional tension.

In this work the attempt to estimate a nitric oxide (NO*) role in regulation of the number of pool haemopoietic stem cells at the irradiated mice was made. With this purpose the number of new compounds from dihydrothiazine-thiazoline line was synthesized, their NO-inhibiting activity was investigated in vivo by the method of ESR-spectroscopy of spin trap and their influence on an output endogenous spleen colonies (CFU-S-8) after the total sublethal y-irradiation of mice in a doze of 6 Gy was also investigated. Was shown, that the tested compounds reduced the contents of NO* in a liver tissue of mice which have received an injection of nitric oxide synthesis inductor - lipopolysaccharide, and also increased an output CFU-S-8 forming endogenous colonies in the spleen of the irradiated mice. Received data testify to perceptivity of search radioprotective agents among NO* synthesis inhibitors.

Synthesis of compounds containing a fragment similar to the guanidine group of L-arginine, which is a substrate of nitric oxide synthase (NOS), is the main direction in creating NOS inhibitors. The inhibitory effect of such compounds is caused not only by their competition with the substrate for the L-arginine-binding site and/or oxidizing center of the enzyme (heme) but also by interaction with peptide motifs of the enzyme that influence its dimerization, affinity for cofactors, and interaction with associated proteins. Structures, activities, and relative in vitro and in vivo specificities of various NOS inhibitors (amino acid and non-amino acid) with linear or cyclic structure and containing guanidine, amidine, or isothiuronium group are considered. These properties are mainly analyzed by comparison with effects of the inhibitors on the inducible NOS.

We studied the effect of NO synthase inhibitor 2-amino-5,6-dihydro-4H-1,3-thiazine (2-ADT) on the cardiovascular system in rats with endotoxic shock. Blood pressure, heart rate, and respiratory rate were recorded. E. coli lipopolysaccharide decreased blood pressure and heart rate. 2-ADT in a dose of 5 mg/kg normalized these hemodynamic parameters. The normalizing effect of 2-ADT decreased with increasing the dose of this preparation. 2-ADT in high doses (10, 20, and 30 mg/kg) and repeated injections of the preparation caused death of experimental animals.

Spatial organization of wild-type (strain U1) tobacco mosaic virus (TMV) and of the temperature-sensitive TMV ts21-66 mutant was compared by tritium planigraphy. The ts21-66 mutant contains two substitutions in the coat protein (Ile21-->Thr and Asp66-->Gly) and, in contrast with U1, induces a hypersensitive response (formation of necroses) on the leaves of plants bearing a host resistance gene N' (for example Nicotiana sylvestris); TMV U1 induces systemic infection (mosaic) on the leaves of such plants. Tritium distribution along the coat protein (CP) polypeptide chain was determined after labelling of both isolated CP preparations and intact virions. In the case of the isolated low-order (3-4S) CP aggregates no reliable differences in tritium distribution between U1 and ts21-66 were found. But in labelling of the intact virions a significant difference between the wild-type and mutant CPs was observed: the N-terminal region of ts21-66 CP incorporated half the amount of tritium than the corresponding region of U1 CP. This means that in U1 virions the CP N-terminal segment is more exposed on the virion surface than in ts21-66 virions. The possibility of direct participation of the N-terminal tail of U1 CP subunits in the process of the N' hypersensitive response suppression is discussed.

The dose response of soluble and membrane forms of angiotensin-converting enzyme to gamma-irradiation is investigated at different pH values of the medium and at different concentrations of acetate-phosphate buffer. Membrane form of the enzyme is more stable shows principally other conformational equilibrium than the soluble form. "Splitted" activation peaks on the curves of the enzyme dose response are observed.

The effect of radioprotectors of different structure on the syntheses of nitric oxide induced by endotoxin in mice was studied. Using ESR-spectroscopy and spin trap techniques, it was shown that compounds of different chemical structure, such as aminothiols, isothiuronium derivatives, thiazolines, indolylalkylamines and others, suppressed the nitric oxide production in a whole body. The analysis of the relevant literature has confirmed the phenomenon described by the authors: radioprotectors show NO-inhibiting activity.

Using the method of electron paramagnetic spectroscopy we demonstrated that thiazine-thiazoline compounds and aminoethyl isothiourea containing the thioamidine group inhibit NO production in the liver of endotoxin-treated mice. Injection of these agents to anesthetized rats increased arterial pressure and enhanced respiration rate. This effect probably reflects inhibition of not only inducible, but also the constitutive synthesis of NO by compounds with thioamidine group.

Capability of S-radioprotectors (AET, 2-AT, 2-ADT) to react with OH-radicals and to protect various molecular biotest systems against radiation damage was compared with that of 5-methoxytryptamine, some amino acids and t-butanol. A method of competing acceptors was used to determine rate constants in reactions of the radioprotectors with OH-radicals. A complex of biotest systems (protein, DNA, protein-lipid complex) was applied to estimate the radioprotective activity in vitro. It was found that the studied S-compounds are capable of modifying the protective effect as compared to the expectation from the competitive kinetics approach. Both enhancing and lessening of the effect was observed depending on the test system used. The obtained results can be explained by the impact of secondary radicals on the bio-target and/or by the interaction of the S-compounds with the bio-target that altered its radiosensitivity.

Mutant ts21-66 of the tobacco mosaic virus (TMV) differs from the wild-type TMV-U1 by two mutations (Ile-21-->Thr and Asp-66-->Gly) in the coat protein (CP) gene and in symptoms produced in infected N' plants. The CP structure in TMV-U1 and ts21-66 virions was probed by tritium planigraphy. Compared with the wild-type CP, labeling of the N-terminal region of mutant CP was half as high and suggested its greater shielding. A role of this CP region in virus interactions with the N' resistance system is discussed.

In experiments with mice radioprotective properties and toxicity of 2(3)-guanidinoalkanethiols were investigated by exposure to gamma-irradiation in the dose of 6.4 Gy. The obtained results allow to find an association between radioprotective activity of 2(3)-guanidinoalkanethiol compounds and their structure and toxicity.

Radiation activation of angiotensin-converting enzyme (respect to Cbz-Phe-His-Leu as substrate) was obtained at the gamma (137Cs, t(irr) = 10s-2h, D approximately 3 Gy)- and X (plasma foces source, t(irr) = 10(-9)s, Cu-filter, D approximately 2 x 10(-5) Gy)-irradiation. The inactivation of the horseradish peroxidase at the same X-irradiation dose (2 x 10(-5) Gy) took place. Based on the experimental data and on the mathematical model proposed by us we made a conclusion that the special points exist on the dose response curves. Besides, the deduction that an activation is a common process at radiation changes of the different enzymes follows from our model. The activation of tobacco peroxidase (in presence of Ca(2+)-cations and without them) and of recombinant horseradish peroxidase (in presence of H2O2) by gamma-irradiation was really observed (respect to guaiacol as substrate).

A study was made of the nature of radiation--induced bonds between DNA and 2-amino-5,6-dehydro-4H-thiazine (2-ADT) having a radioprotective action. Using the gelfiltration method and 35S-2-ADT, it was shown that the amount of the radioprotector bound to DNA increased with radiation dose and did not depend on the postirradiation treatment with 3 M LiCl or 3 M urea. No marked binding was noted after mixing the separately exposed DNA and the protector. It is concluded that a covalent linkage of DNA and 2-ADT occurs, upon irradiation, via short-living states of DNA and (or) the protector.