[Radioprotective properties of isothiourea derivatives with NO-inhibitory mechanism of action].

The study of the radioprotective activity of S-[2-alkyl (aryl) sulfonyl]-S-ethyl derivatives of (vinyl)-isothiourea in (he model of the survival of mice exposed to gamma-radiation at a dose of 10 Gy has shown that the incorporation of additional sulfur-containing groups does not increase the radioprotective properties of compounds. In contrast to aminoalkil thiols, the effectiveness of the radiation protection action of the isothiourea (ITU) derivatives studied clearly correlates with the NO-inhibitory activity. This fact allowed us to assume that the radioprotective effect of S-substituted ITU caused inhibition of the endogenous synthesis of NO, which promotes the development of circulatory hypoxia, and that a further search for the radioprotective agents in this class of chemicals should be considered as the search for effective inhibitors of NO-synthase (NOS). The theoretical analysis of the conformity of molecular structures to the composition and topology of the active center of NOS-inhibitors allowed us to prognosticate a number of new ITU derivatives with the potential NOS-inhibiting ability. As a result of further theoretical and experimental studies, four S,N-disubstituted ITU derivatives - active non-selective NOS-inhibitors, were first identified and synthesized. These compounds exhibited a pronounced and prolonged vasopressive effects at doses of 0.01-0.05 LD50/15 in the models of severe hemorrhagic and endotoxic shock, and provided 65-100% 30-day survival at doses of 0.2-0.3 LD50/15 in the mice irradiated by gamma-rays at a dose of 10 Gy (LD98/30).The findings suggest the pronounced radioprotective effect of NOS-inhibitors among the ITU-derivatives.

[Effect of increased mechanical loading on the relation between the contraction of isolated cardiac muscle and the concentration of Ca++ in the perfusate]. / Vliianie povyshennoi mekhanicheskoi nagruzki na zavisimost' sokrashcheniia izolirovannoi serdechnoi myshtsy ot kontsentratsii Ca++ v perfuzate.

The distension of isolated papillary muscles working isotonically or a transition to isometric working entailed an increased sensitivity of the contractile velocity to changes in perfusate Ca++ concentration. After sudden fall in Ca++ concentration, a more rapid decline of the contractile velocity in isometric mode was observed as compared to isotonic mode of working. The similar difference was found in experiments on isolated guinea pig heart working in isovolumic or auxotonic modes, though the rate of Ca++ loss by the heart was the same. The results suggest that an increased mechanical load may diminish the ability of myocardial cells to compensate for the changes in external Ca++.

[Protective effect of extracellular K+ in the myocardium in disorders of energy metabolism]. / Zaschitnyi éffekt vnekletochnogo K + v miokarde pri narushenii énergoobrazovaniia.

In an experimental study on isolated isovolumetric guinea-pig hearts, a 2.2-fold reduction of the coronary duct combined with metabolic block caused by dinitrophenol (0.05 mM) resulted in an eleven-fold drop in the attained pressure, and a shorter electric systole, a smaller P wave, and an ST displacement on the ECG. Deep suppression of mechanical and electric activity was combined with reduced glycogen content, and greater K+ and Na+ withdrawal from the heart. Quantitatively, the drop in contractility correlated with K+ withdrawal and ST displacement. A sudden increase in coronary perfusion rate was accompanied by a rapid increase in the rate of K+ elimination from the heart which was proportionate to the rate of hyperfusion, with a simultaneous transitory rise in attained pressure, a great increment in diastolic pressure and the emergence of arrhythmia and fibrillation, the severity of the changes correlating with the degree of K+ loss. A moderate increase in K+ concentration of the perfusate prevented the development of fibrillation and drastically reduced the degree of contracture and glycogen drop during hyperfusion. The obtained results suggest that moderate accumulation of extracellular K+ during the early phase of energy generation disorder can be of a protective nature, as it contributes to a sharp reduction in contractility and energy spending to improve cell survivability in critical conditions.

[Fast and highly-sensitive method of quantitative determination of carnosine and anserine in animal tissues]. / Bystryi i vysokochuvstvitel'nosti metod kolichestvennogo opredeleniia karnozina i anzerina v tkaniakh zhivotnykh

A method is described for separation of carnosine and anserine and of the amino acids constituting them by means of thin-layer chromatography. For quantitative estimation the amino acids and dipeptides were treated with 7-chlorine-4-nitrobenzeno-2-hydroxy-1,3-diazol (NBD-chloride) and subsequently separated by chromatography on silica gel and estimated by absorption at 456-470 nm. Systems of solvents were developed for separation of both free and chemically modified amino acids and dipeptides; optimal conditions were chosen for preparation of tissue extracts and their treatment with NBD-chloride. By this method carnosine and anserine could be stimated in extract from 0.02-0.2 mg of muscular tissue. The time required for the analyses was about 3-5 hrs.