[SQUALENE: PHYSIOLOGICAL AND PHARMACOLOGICAL PROPERTIES].

The review of literature demonstrates that squalene, known to most experts as an intermediate product in the synthesis of cholesterol, has several pharmacological properties including hypolipidemic, hepatoprotective, cardioprotective, antioxidant, and antitoxicant activity. Squalene is effective in the treatment of diabetes mellitus type 2 and can potentiate the activity of some antitumor (antiblastoma) preparations and reduce their undesired side effects. This bioactive substance has low toxicity and, in therapeutic doses, does not produce any damaging action on the human organism. A promising source of raw material for the commercial production of squalene is offered by amaranth seed oil.

[The influence of application of a low-frequency magnetic field on the serum corticosterone level (an experimental study)].

The results of analysis of the literature publications suggest the necessity of experimental studies aimed at investigation of modulating effect of low-frequency magnetic fields on endocrine organs. The present study was carried out using 200 outbred white male rats (body weight 200-220 g). Corticosterone was measured in blood sera following the application of a low-frequency magnetic field (20 and 53 Hz with induction from 0.4 to 6 mT) generated by a Mini-Expert-T apparatus for induction magnetic therapy during 30 minutes. It was shown that the application of the alternating magnetic field to the adrenal region of the rats in the selected frequency and induction ranges caused a significant increase in the serum corticosterone levels. The results of the present study on the hormonal activity of rat adrenals give reason to consider the influence of the alternating magnetic fields as being modulatory. Analysis of the data thus obtained has demonstrated the non-linear dependence of glucocorticoid activity of the rat adrenal glands on the induction strength of the alternating magnetic field.

[Medium molecular size peptides of blood plasma in diabetes mellitus].

The level of medium molecular peptides (MMP) grows up in blood plasma of patients with diabetes mellitus (DM), which results in endogenous intoxication. The MMP concentration is high in patients with insulin-independent DM at compensation and without renal affection versus insulin-dependent DM, which is explained by presence of 1-3 kDa peptides. An aggravated course of DM including subcompensation is associated with a higher MMP level in patients with both DM types. The onset of the initial stage of diabetic nephropathy brings about an essential decrease of all MMP fractions in both DM types.

[Mean molecule peptides of plasma and blood serum].

The concentration of mean molecule peptides is by far less in serum versus plasma. The concentration of mean molecule peptides in serum can go down, in endotoxicosis degrees 3-4, to normal values, whereas it can exceed 3-4-fold the normal value in plasma. The most pronounced reduction of peptides' concentration in serum was registered for the fraction with the molecular weight ranging from 800 to 3000 D.

[Some mechanisms of adenosine protective effect in the "calcium paradox"]. / Nekotorye mekhanizmy zashchitnogo deistviia adenozina pri kal'tsievom paradokse.

A possibility of preventing the "calcium paradox" with the aid of adenosine was studied as well as some mechanisms of adenosine effect upon the heart in case of the "calcium paradox". Adenosine was found to suppress release of amino acids from the heart in perfusion with calcium-free medium, to efficiently prevent disorders in the energy-dependent functions of mitochondrion and myoglobin release from the heart in reperfusion with Ca2+ -containing solution. Adenosine was also found to increase 2-10-fold lactate release from the heart. Adenosine seems to be able to activate glycolysis. Iodine acetate was shown to completely suppress the adenosine ability to decrease amino acid release from the heart perfused with calcium-free medium. Under conditions of iodine acetate blocking of glycolysis was found to possess no protective properties against cytolysis in the "calcium paradox". The heart mitochondria isolated in the end of the experiment revealed low values of free or phosphorylating respiration and complete dissociation of oxidation. Also a protective effect of adenosine in inhibition of Na+, K+ -ATPhase with Strophantinum, was studied.

[Dependence of myocardial contracture on energy resources during the calcium paradox]. / Zavisimost' kontraktury miokarda pri "Kal'tsievom paradokse" ot énergeticheskikh resursov.

Perfusion of the rat isolated hearts with calcium-free and calcium containing solution revealed a complex and deep myocardial damage called the calcium paradox. The reperfusion of the rat heart with calcium rich media resulted in myoglobin loss from the heart, significant decreasing of ATP and phosphocreatine level, complete uncoupling of respiration and phosphorylation in mitochondria, occurrence of myocardial contracture. Decreasing of sodium level to 30 mM--80 mM in calcium free media exacerbates the heart damage due to the calcium paradox with absence of contracture. Addition of phosphocreatine (1 mM, 5 mM, 10 mM) evoked some restoration of ATP contents in the tissue with appearance of significant contracture. Phosphocreatine exacerbated the loss of myoglobin from the heart subjected to the calcium paradox. A discrepancy between myocardial contracture and degree of cellular damage has been observed during the calcium paradox.

[Dependence of myocardium injury on extracellular K+ concentration during calcium paradox]. / Zavisimost' povrezhdenii serdtsa ot vnekletochnoi kontsentratsii K+ pri "kal'tsievom paradokse".

It is well-known that the first stage of the calcium paradox involves decreasing of Na+ gradient. The decreased sodium gradient is a cause of activation of the Na(+)-Ca+ exchange and formation of cardiac injury during the calcium repletion. Potassium ions are natural extracellular activators of Na(+)-pump. It has been shown that heart perfusion by Ca(2+)-free medium evoked extrusion from cells of hydrophilic amino acids whose transport-depends on sodium gradient. The heart reperdusion with Ca(2+)-containing agent leads to myofibrillar contracture and extensive myoglobin release. The simultaneous events are: elevation in tissue water contents, decreasing of intracellular concentration of adeninnucleotides, uncoupling of oxidation and phosphorylation in mitochondria. The decreasing of K+ level to 0.5 mM exacerbates myocardial damage during the calcium paradox, despite absence of myocardial contracture. The elevation of K+ (to 10 mM or 20 mM) attenuated the calcium paradox development in the heart. The elevated K+ concentration protected isolated heart from extensive myoglobin release, development of myocardial contracture. The high K+ concentrations alleviate mitochondrial damage and elevate contents of adeninnucleotide in the tissue. The positive effect of the elevated K+ concentration can be completely blocked by strophanthine, the selective Na+, K(+)-pumb blocker.

[Mechanisms of action of hypersodium medium on contractile activity of isolated rat heart]. / Mekhanizmy vliianiia gipernatrievoi sredy na sokratitel'nuiu aktivnost' izolirovannogo serdtsa krys.

Despite the high efficiency of elevated concentrations of sodium ions during myocardial ischemia and calcium paradox, the molecular mechanism of action of hypersodium media on heart contractions remains unknown. The purpose of the investigation was to study mechanisms by which raised concentrations of sodium ions alter cardiac contractility. Subsequent to initially developed reduced pressure in the left ventricle, elevated concentrations of sodium ions (200 mM instead of 140 mM NaCl, 3 mM KCl) produced an increased force of contractions of about 50%. The first stage of decrease in developed pressure did not relate to elevated tonicity of extracellular ionic millieu because lithium chloride (60 mM) did not produce the same effect. This action of elevated concentrations of sodium ions has been shown to be independent of blockers of ion-transporting systems (caffeine, verapamile, ethmozine, HMA or lidocaine). Raising the contractions by elevating the concentration of sodium ions (second stage) has been shown to be susceptible to sodium channel blockers (6-IA, benzamil, of phenamil) and to caffeine. Decreasing of potassium concentration (from 3 mM to 1-2 mM amplified, and increasing of K+ level (from 3 mM to 6 mM) attenuated the positive inotropic action of the elevated concentration of sodium ions. The positive inotropic effect due to elevated concentrations of sodium ions remains even after heart arrest by high concentrations of verapamile (2 mcM). Lithium chloride (60 mM) failed to elevate left ventricle developed pressure which was raised by elevated concentrations of sodium ions. These data suggest that the elevated concentration of sodium ions could effect Na+/Ca2+ exchange and provoke Ca2+ release from sarcoplasmic reticulum by changing the sodium gradient and resulting in Ca2+ entry via Na+/Ca2+ exchange. These observations are consistent with the hypothesis of Leblanc N., Hume J.R. (1990) regarding sodium-induced calcium ion release from sarcoplasmic reticulum.

[Effect of antioxidant histochrome preparation on the contractile function and metabolism of the isolated rat heart under conditions of "calcium paradox", ischemia, and reperfusion]. / Vliianie antioksidantnogo preparata gistokhrom na sokratitel'nuiu funktsiiu i metabolizm izolirovannogo serdtsa krysy v usloviiakh "kal'tsievogo paradoksa", ishemii i reperfuzii.

A comparative study of protective effect of a new antioxidant histochrome on isolated rat heart at calcium paradox and ischemia-reperfusion was carried out. Perfusion with Ca-containing solution after 10-min perfusion with Ca-free medium caused depletion of high energy phosphates, loss of myoglobin, uncoupling of mitochondria, increase of left ventricular diastolic pressure. Pretreatment with histochrome led to decrease of cardiomyocyte damage evaluated by myoglobin efflux in perfused solution, attenuation of decrease ATP and phosphocreatine, and coupling of mitochondria. This resulted in a decrease of left ventricular diastolic pressure at calcium paradox. Less effect of histochrome treatment was noted in the case of ischemia-reperfusion model. It was concluded that histochrome effectively prevents heart from abnormalities caused by calcium imbalance in heart.

[The importance of the ion-transport systems of the sarcolemma and sarcoplasmic reticulum in changing rat cardiac contractile function under a hypersodium medium]. / Znachenie nekotorykh ionotransportnykh sistem sarkolemmy i sarkoplazmaticheskogo retikuluma v izmenenii sokratitel'noi funktsii serdtsa gipernatrievoi sredoi u krys.

Following a reduced pressure in the left ventricle, elevated concentrations of sodium ions enhanced by half the contraction force of the rat isolated heart. This effect was shown to be independent of the Na-channels blockers or Na/H exchange of caffeine but quite susceptible to sodium channel blockers, caffeine, and the blocking agent for Na-Ca exchange Ni2+. A decrease in potassium concentration amplified, and elevation of K+ level attenuated the positive inotropic effect of the elevated concentration of sodium ions. The effect was preserved even after heart arrest induced by verapamil. The findings suggest that elevated concentration of sodium ions may affect the Na+/Ca2+ exchange and provoke Ca2+ release from sarcoplasmic reticulum by means of changing the sodium gradient. These data corroborate the Leblanc and Hume hypothesis of the sodium-induced calcium ions release from sarcoplasmic reticulum.

[The role of ion transport system of sarcolemma in amino acid loss during myocardial perfusion with calcium-free medium and myocardium injury during "calcium paradox"]. / Rol' ionotransportnykh sistem sarkolemmy v potere aminokislot pri perfuzii serdtsa beskal'tsievoi sredoi i povrezhdenii miokarda pri "kal'tsievom paradokse".

The loss of myocardial amino acids is known to depend on sodium gradient across sarcolemma. This is regulated by changes of cellular volume as well. It is suggested that loss of amino acids can be regulated by blocking of anion-transporting systems during Ca-free perfusion. It have been found that calcium depletion from extracellular medium exacerbates release of amino acids two- four fold. Sodium lowering (from 140 mM to 30 mM) accelerates and sodium elevation (from 140 mM to 200 mM) attenuates loss of taurine, glutamine, glycine, glutamate, aspartate, alanine and asparagine, but does not hydrophobic amino acids. Inhibition of CI- channels by IAA94 or K-Cl cotransport with DIOA increases the loss of taurine, glutamine, glycine, glutamate, aspartate, alanine and asparagine during Ca-free perfusion. The release of amino acids during Ca-free perfusion is negatively correlated with recovery of oxidative phosphorylation during the second phase the calcium paradox-Ca-readmission.

[Effect of the ion composition of the calcium-free medium and cardiomyocyte damage during "calcium paradox" in rats]. / Vliianie ionnogo sostava beskal'tsievoi sredy i povrezhdeniie kardiomiotsitov krys pri kal'tsievom paradokse.

The findings reveal that the degree of myocardial damage in the "calcium paradox" does not depend on the contracture strength, that the contracture attenuation due to a decreased concentration in the Ca-free medium is not equal to the cardiocytes protection as compared with other means. Mg2+ and the studied means of myocardial protection seem to play a major role in assessment of the "calcium paradox" development and explain the difference in results of the hyposodium medium effects in the "calcium paradox".

[Dependence of myocardial damage on the anion composition and osmotic pressure in the extracellular fluid during "calcium paradox" in rats]. / Zavisimost' povrezhdenii serdtsa krys pri "kal'tsievom paradokse" ot anionnogo sostava i osmoticheskogo davleniia vnekletochnoi sredy.

The data obtained reveal that elevation of extracellular osmolarity with sucrose during reintroduction of Ca-containing medium after 10 minutes of Ca2+ removal prevents loss of haemoglobin in a concentration-dependent mode. Reducing the extracellular osmolarity of the reperfusion medium by means of decreasing the concentration of sodium chloride and calcium chloride exacerbates the loss of haemoglobin from the cardiomyocytes. There is a close correlation between the water contents in tissues and the loss of haemoglobin during the "calcium paradox". The findings suggest dependence of the heart damage during the "calcium paradox" on anionic composition of extracellular space and activity of anionic transporters.

[Dependence of the protective effect of the elevated sodium level on the type of oxidative substrate in the isolated heart during "calcium paradox"]. / Zavisimost' zashchitnogo deistviia gipernatrievoi sredy ot vida substrata okisleniia v tselom serdtse pri kal'tsievom paradokse.

Isolated guinea pig heart were perfused with the Tyrode solution followed in 15 min. by a 10-min. Ca(2+)-free solution with subsequent return to the normal Ca(2+)-containing Tyrode solution. Sarcolemma damage was measured by myoglobin release. The perfusion resulted in damage of the myocardium cells. The data obtained show that elevation of the extracellular pressure during reperfusion with the Ca(2+)-containing medium is more important than the absolute value of the osmotic pressure.

[Dissociation between the development of myocardial contracture and heart damage in the "calcium paradox"]. / Nesootvetstvie mezhdu razvitiem kontraktury miokarda i povrezhdeniem serdtsa pri "kal'tsievom paradokse".

The interrelationship between contracture development and heart damage during the calcium paradox under different sodium concentration in Ca-free media was studied on isolated rat hearts. It had been shown that calcium paradox development accompanied contracture development, intensive membrane disruption and alteration of tissue energy state. We had not found relation between contracture magnitude and degree of myocardial alterations in calcium paradox. Our dates confirm so-called intracellular hypothesis of calcium paradox. The experiments had shown close correlation between transmembrane sodium gradient in Ca-free media and degree of cellular damage and energy state alterations during calcium readmission in solution.

[Effect of extracellular concentration of sodium on swelling of cardiomyocytes and myocardial damage during calcium paradox]. / Vliianie vnekletochnoi kontsentratsii natriia na velichinu nabukhaniia kardiomiotsitov i povrezhdenie cerdtsa pri "kal'tsievom paradokse".

The aim of investigation was to study the effects of extracellular sodium concentration on cardiomyocyte swelling and evaluation of this process in myocardial damage due to the calcium paradox. The experiments on isolated rat hearts showed that reperfusion by Ca- containing solution (Ca2+ 2.0 mM) after 10 minutes perfusion with Ca- free medium caused ameliration of water contents, depletion of high-energy phosphates, loss of myoglobin and uncoupling of respiration and phosphorylation in mitochondria. Either decreasing of sodium concentration (till 30-80 mM) or addition of strophant-hine (50 microM) resulted in exacerbation of calcium paradox (further augmentation of tissue water contents and increasing of cellular damage). Sucrose (240-340 mM), added low-sodium Ca- free solution was failed to prevent accumulation of water, loss of myoglobin and high- energy phosphates caused by subsequent perfusion with Ca- containing medium. Elevation of extracellular concentration of sodium ions (from 140 mM till 200-220 mM), but did not tonicity reduced cellular swelling, water accumulation in tissue, prevented loss of myoglobin and ATP, phosphocreatine level. The protective effect of hypersodium medium remained unchanged even sucrose was added to reperfusion solution to maintain osmotic pressure throuthout experiment. There are close correlation between intensity of water accumulation and degree of myocaridal damage during the calcium paradox, that confirms participant of Na- dependent cellular swelling in the development of cellular abnormalities due to calcium paradox.