[Phase analysis of the cardiac cycle in patients with arterial hypertension based on the results of equilibrium radioventriculography].

AIM: To study cardiac cycle parameters in patients with grade I and II AH by equilibrium radioventriculography (ERVG) and the possibility of using them for diagnostics of systolic and diastolic myocardial dysfunction. MATERIALS AND METHODS: Left and right ventricular diastolic and systolic functions were evaluated by conventional ERVG using a MB-9100 gamma-chamber (Gamma, Hungary) and the Gold-Rada+ system for data collection and processing. The study involved 142 patients divided into 3 groups. Group 1 included 38 patient with grade 1 AH (mean age 20.7 +/- 6.2 yr), group 2 85 patients with grade II AH (58.7 +/- 10.7 yr), group 3 19 practically healthy subjects (29.4 +/- 10.8 yr). RESULTS: No significant abnormalities in hemodynamic characteristics except increased filling of the right ventricle for 1/3 diastole were observed in group 1. Decreased filling for 1/3 diastole, maximum filling rate, and the ratio of filling to ejection rates were revealed in group 2. In order to counterbalance HR differences, the time-related ERVG values were calculated per RR interval; it allowed to reveal diastolic disorders confirmed in the study of ERVG "hemodynamics characteristics. Patients with grade II AH showed a longer time of maximum filling rate with respect to left and right ventricular RR intervals compared with controls. In group 1, this parameter was lower than in healthy subjects.

[Changes of spiroergometric parameters in males under 30 years of age with a hypertensive reaction of arterial pressure to graduated exercise].

UNLABELLED: AIM. To study changes in blood pressure (BP) and spiroergometric parameters in 18-30-year-old males with normal BP at rest having different reactions of BP to graduated exercise. MATERIAL AND METHODS: Forty two male examinees performed treadmill-test according to R. Bruce protocol with measurements of BP, ECG parameters and gas composition of exhaled air. RESULTS: The treadmill test has shown that 20 (47.6%) males had a normotensive reaction of BP to exercise, 22 (52.4%)--a hypertensive reaction. The latter had higher systolic and/or diastolic BP levels than those normal for performance of treadmill test. Significantly higher were also parameters of pulmonary ventilation, oxygen pulse in combination with large consumption of O2 and expiration of CO2. CONCLUSION: The presence of significant differences by spiroergometric indices in males with normotensive and hypertensive reactions of BP to exercise but normal BP at rest reflects metabolic shifts at early stages of hypertension in the latter.

[Local myocardial contractility in patients with coronary heart disease and chronic heart failure].

The aim of the study was to evaluate the peculiarities of local left and right ventricular myocardial contractility in patients with coronary heart disease (CHD) and various degrees of chronic heart failure (CHF) using biventricular radioventriculography (RVG). Local left and right ventricular myocardial contractility was evaluated in 127 patients with CHD and CHF using RVG with a standard procedure of segmentary and phase histogram analysis. The patients were divided into two groups according to left ventricular ejection fraction (LVEF). Group I consisted of 89 CHD patients with NYHA II-III CHF and LVEF of > 40%; group II included 38 CHD patients with NYHA III-IV CHF and LVEF of < 40%. The significant decrease of LVEF in group II was caused by the prevalence of hypo- and akinetic segments in the structure of local contractility. In both groups total LVEF was maintained by lateral wall segments. Right ventricular contractility in patients with CHD and CHF was maintained by anteroseptal segments.

Protoreaction of protoplasm.

My goal is to describe briefly the universal cellular reaction (UCR) to external actions and agents. This general reaction was the main subject of investigation by the scientific school of the outstanding Russian cytologist, Dmitrii Nasonov (1895-1957). The UCR consists of two phases of complex changes in cellular viscosity and turbidity, in the cell's ability to bind vital dyes, in the resting membrane potential, and in cellular resistance to harmful actions. Works from the Nasonov School have shown that these changes are based on structural-functional transformations of many cell proteins that react uniformly to actions of different physical and chemical nature. In general, these complex changes do not depend on cell type, indicating the universal and ancient nature of the UCR as well as its general biological significance. A new interpretation of the mechanism of the universal reaction is proposed in this paper, and a possible role for contractile proteins in the mechanism of the UCR of muscle cells is presented. In addition, the concept of cell hydrophobicity is introduced. Nasonov's School proposed a concept of physiological standardization that allows comparison of data obtained by different investigators and that will also be described here.

"Fathers" and "sons" of theories in cell physiology: the membrane theory.

The last 50 years in the history of life sciences are remarkable for a new important feature that looks as a great threat for their future. A profound specialization dominating in quickly developing fields of science causes a crisis of the scientific method. The essence of the method is a unity of two elements, the experimental data and the theory that explains them. To us, "fathers" of science, classically, were the creators of new ideas and theories. They were the true experts of their own theories. It is only they who have the right to say: "I am the theory". In other words, they were carriers of theories, of the theoretical knowledge. The fathers provided the necessary logical integrity to their theories, since theories in biology have still to be based on strict mathematical proofs. It is not true for sons. As a result of massive specialization, modern experts operate in very confined close spaces. They formulate particular rules far from the level of theory. The main theories of science are known to them only at the textbook level. Nowadays, nobody can say: "I am the theory". With whom, then is it possible to discuss today on a broader theoretical level? How can a classical theory--for example, the membrane one--be changed or even disproved under these conditions? How can the "sons" with their narrow education catch sight of membrane theory defects? As a result, "global" theories have few critics and control. Due to specialization, we have lost the ability to work at the experimental level of biology within the correct or appropriate theoretical context. The scientific method in its classic form is now being rapidly eroded. A good case can be made for "Membrane Theory", to which we will largely refer throughout this article.

[Cell shrinkage during apoptosis is not obligatory. Apoptosis of U937 cells induced by staurosporine and etoposide]. / Degidratsionnoe sokrashchenie ob"ema kletok pri apoptoze--fakul'tativnyi priznak. Apoptoz kletok U937, vyzvannyi staurosporinom i étopozidom.

A study was made of apoptotic cell shrinkage, which is generally believed to be a hallmark of apoptosis. The two conventional models of apoptosis were used for examination of changes in cell water balance--one is apoptosis caused in human lymphoma cell line U937 by staurosporine, and the other by etoposide. Intracellular water was determined by measuring buoyant density of cells in continuous Percoll gradient. Apoptosis was recognized by microscopy and flow cytometry. Apoptosis caused by staurosporine (1 microM, 4 h) was found to be associated with a decrease in cell water content by almost 24%. In contrast, no decrease in cell water content was observed in U937 cells incubated with etoposide (50 microM, 4 h), in spite of the number of features suggesting the presence of apoptosis, such as the appearance of apoptotic bodies, chromatin condensation and fragmentation and disappearance of S-phase cells in DNA histogram. It is concluded that definition of apoptosis as "shrinkage-necrosis" (Kerr, 1971) needs correcting: the distinction of apoptotic cells involves the absence of swelling, rather than cell shrinkage.

[Water and ion balance in rat thymocytes under apoptosis induced with dexamethasone or etoposide. Ion-osmotic model of cell volume decrease]. / Vodnyi i ionnyi balans timotsitov krysy pri apoptoze, vyzvannom deksametazonom i étopozidom. Iono-osmoticheskaia model' umen'sheniia ob'ema kletki.

Cell ion and water balance was studied with respect to analysis of the osmotic model of apoptotic volume decrease (AVD) in rat thymocytes under dexamethasone (1 microM, 4-6 h) or etoposide (50 microM, 5 h) treatment. Intracellular water content was determined by measurement of cell buoyant density in continuous Percoll gradient, while intracellular potassium and sodium contents were determined by flame emission analysis. Apoptosis was verified by an increase in cell buoyant density, fluorescence of cells stained with Acridine orange and Ethidium bromide (flow cytometry), by changes in the cell cycle and the appearance of sub-diploid peak in the DNA histogram (flow cytometry), and by a decrease in cell size examined with light microscope. A separate fraction of dense cells with reduced size was found to appear after dexamethasone or etoposide treatment. This fraction was considered as apoptotic. An increase in buoyant density of apoptotic cells corresponded to a decrease in cell water content. In apoptotic cells vs. cells with normal buoyant density, the intracellular potassium content was lower, but sodium content was higher. The sum of potassium and sodium contents was lower in apoptotic cells. Taken into account the loss of anions, associated with the loss of cations, the bulk decrease in ions content has been sufficient to be accounted for cell volume decrease on the basis of the ion-osmotic model.

[Painless myocardial ischemia as a risk factor of constantly relapsing paroxysms of cardiac fibrillation]. / Bezbolevaia ishemiia miokarda kak faktor riska nepreryvno retsidiviruiushchikh paroksozmov mertsatel'noi aritmii.

A case is reported illustrating relationship between marked coronary atherosclerosis with development of painless myocardial ischemia (PMI) and constantly recurrent paroxysms of cardiac fibrillation (CF). A male 62-year-old patient suffering from paroxysmal CF received cordaron in a dose 200 mg twice a day. The treatment was ineffective until a comprehensive examination (thyroid hormones, echocardiography, Holter ECG monitoring, treadmill test, CT of the coronary arteries) found PMI episodes and severe stenosing atherosclerosis and the treatment was changed for sotalex (80 mg twice a day). Sotalex treatment was effective and stopped recurrences of CF.

[Effects of perstarium on the systolic and diastolic functions of the myocardium in patients with chronic cardiac failure]. / Vliianie prestariuma na sistolicheskuiu i diastonicheskuiu funktsii miokarda u bol'nykh s khronicheskoi serdechnoi nedostatochnost'iu.

The aim of the study was to assess prestarium effects on systolic and diastolic cardiac functions in 38 patients with ischemic heart disease and chronic cardiac failure (NYHA functional class II-IV) by biventricular balanced radioventriculography. Both left and right ventricular diastolic dysfunction was found. A course of prestarium treatment caused different alterations in ventricular contractility. 64.2% patients of those who had right ventricular ejection fraction < 40% achieved an increase in right and left ventricular ejection fraction. Improved diastolic function of the myocardium was registered in 71% patients.

[Study of "group" expression of mRNA of the ion transporters ATP1B1, NHE1 and NKCC1, beta-actin, glycerophosphosphate dehydrogenase, proteins regulating proliferation and apoptosis of p53, Bcl-2, IL-2 and hSGK kinase at the prereplicative stage of human lymphocyte activation]. / Issledovanie "gruppovoi" ékspressii mRNK ionnykh transporterov ATP1B1, NHE1 i NKCC1, beta-aktina, glitserofosfatdegidrogenazy, belkov--reguliatorov proliferatsii i apoptoza p53, Bcl-2, IL-2 i kinazy hSGK na predreplikativnoi stadii aktivatsii limfotsitov cheloveka.

Previously, we found no segregation in F2 obtained from crosses between two Dileptus anser clones differing (under the same culture conditions) in their serotypes, i.e. in their immobilization antigens (i-antigens); indeed, all the F2 clones had mixed, i.e. hybrid serotype, being immobilized simultaneously with both immune sera developed against either parental clone (Uspenskaya, Yudin, 2000). Presently, experiments were carried out to see if this unusual phenotype would be re-expressed after a temporary switching off. To switch off both expressed i-antigens, serotype transformation was induced in the F2 clones by shifting the culture temperature from 25 to 17 degrees C. Two weeks later, when the clones returned to the initial temperature conditions, each of them was seen to re-express both parental i-antigens. This result is discussed with reference to the role of i-antigens in regulation of their own expression as has been suggested by some authors.

Differential transcription of ion transporters, NHE1, ATP1B1, NKCC1 in human peripheral blood lymphocytes activated to proliferation.

This work, using RT PCR, studied expression of mRNAs encoding ion transporters, the Na/H antiporter (NHE1), the beta subunit of the Na,K-ATPase pump (ATP1B1), the NaK2Cl symporter (NKCC1), and some proteins unrelated to ion transport: the serum and glucocorticoid dependent kinase (hSGK), beta-actin, a glycolytic enzyme (GAPDH), and regulators of proliferation and apoptosis (p53, Bcl-2) during activation of human lymphocytes with phytohemagglutinin for 4-24 h. Within 24 hours the mRNA levels of NHE1, beta-actin, Bcl-2, and p53 increased by more than 100%, the mRNA levels of ATP1B1, GAPDH, and hSGK, by about 50%, while the mRNA levels of NKCC1 decreased transiently. These results indicate a differential transcriptional control of NHE1, ATP1B1, and NKCC1 following a proliferative stimulus of human lymphocytes.

Evidence of a new type of protein-protein interaction: desensitized actomyosin blocks Ca(2+)-sensitivity of the natural one. A possible model for an intracellular signalling system related to actin filaments.

Actin filaments are certainly believed to function as an intracellular signalling system; however, this is not confirmed by direct evidence. We used a two-layer actomyosin gel with a concentration gradient of the troponin-tropomyosin complex (TT-complex, Ca(2+)-sensitive system) between the two layers. To prepare one layer of the system, natural actomyosin (nAM) rich in TT-complex was used. To prepare the second layer, we used desensitized actomyosin (dAM) without the complex. All experimental studies were made in medium with a low ionic strength. Two phenomena were observed: (1) dAM blocks Ca(2+)-sensitivity of nAM when the dAM weight portion in the system (as well as in mixed nAM + dAM suspension) reaches 40% and more; further increase of the dAM portion does not affect the Ca(2+)-sensitivity; (2) it was electrophoretically shown that a rapid diffusion of the TT-complex from nAM gel into the dAM gel took place. The apparent diffusion coefficient for the TT-complex in dAM gel is about (1-4).10(-4) cm2/sec, i.e. three orders higher than the same values for protein diffusion in water.

[Effect of ethanol and polyethylene glycol-400 on frequency dependence of the inotropic effect of verapamil on the frog myocardium]. / Vliianie étanola i poliétilenglikolia-400 na chastotozavisimost' inotropnogo deistviia verapamila na serdechnuiu myshtsu liagushki.

The PEG-400 was found to be neutral in respect to the frequency-dependent V negative inotropic action whereas ethanol enhanced this dependence. The findings suggest a possibility for V inotropic activity to be modified by lipophilic agents, provided they sterically complementary to hydrophobic domains of the Ca2(+)-channel structure.

[Hydrophobic interactions as the basis of the inotropic effect of verapamil]. / Gidrofobnye vzaimodeistviia kak osnova inotropnogo éffekta verapamila.

The role of hydrophobic interactions (HI) of verapamil (V) in the mechanism of its blocking action on voltage-dependent Ca(2+)-channels was considered. For this purpose a comparative study of V inotropic effects and general anesthetics (GA) modeling V action on rhythmic switches of frog heart muscle was made. Concentration thresholds of the agents of inotropic action (Cth) were determined at two frequencies of stimulation, 4 and 30 switches per minute, resp. According to features of the inotropic action the studied agents were divided into two groups: Cth values of the former group were dependent on stimulation frequency (V, methanol, ethanol, isopropanol, chloral hydrate and acetone); Cth values of agents of the latter group were independent on stimulation frequency (n-butanol, n-pentanol, n-hexanol, and chloroform). In both groups Cth values were linearly dependent on agent hydrophobicities (in logarithmic scale). It indicates that HI play the main role in interaction of the studied agents with biostructures and primarily with protein structures of Ca(2+)-channels, which are targets for V-like ligand action. The results obtained make an experimental support of our earlier proposed "hydrophobic" model of blocking action of V on plasmalemmal L-type Ca(2+)-channels.

[Effect of verapamil and anesthetics on the level of sodium and potassium ions in frog muscles. Role of hydrophobic interactions]. / Vliianie verapamila i anestetikov na soderzhanie ionov natriia i kaliia v myshtsakh liagushki. Rol' gidrofobnykh vzaimodeistvii.

Verapamil, general and local anesthetics influences on ionic contents of frog sartorius and cardiac muscles in respect with these drugs hydrophobicity were studied to clarify the role of verapamil hydrophobic interactions in its physiological activity. It was found that concentration thresholds of the agents toxicities were linearly linked with their hydrophobicity (in logarithmic scale). This relationship provides support for our conclusion that verapamil, general and some local anesthetics are the members of a single drug family. It is a reason to believe that a hydrophobic mechanism of general anesthetic action on cellular structure is the same as a mechanism of verapamil activity in muscles. It is possible that verapamil is accepted as medical drug exactly due to optimum combination of high verapamil hydrophobicity with its structural complementarity to receptor site responsible for use-dependent channel blocking.

[Changes in the adhesion between enterocytes in short-term exposures to blastomogens, retinol acetate and indomethacin]. / Izmenenie stseplennosti mezhdu énterotsitami pri kratkovremennykh vozdeistviiakh blastomogenov, retinola atsetata i indomteatsina.

The study was concerned with the effect of carcinogens and anticarcinogens on the rate of cell loss in the large bowel epithelium of mice. Intestinal carcinogens such as N-methyl-N-nitrosourea and 1.2-dimethylhydrazine were shown to cause a long-lasting decrease in enterocyte loss. Conversely, retinol acetate and indomethacin treatment enhanced cell loss both under normal conditions and in the presence of the carcinogens. The protective effect against N-methyl-N-nitrosourea was more apparent than against 1.2-dimethylhydrazine. The effect was more pronounced in Balb/c mice compared to AKR/J. A close correlation between the protective and the anticarcinogenic effects of the drugs was established. The data obtained suggest that retinol acetate and indomethacin cause reversion of specific early reaction of the large bowel epithelium to carcinogens and are most effective in application in the promotion phase of carcinogens.

[Changes in the adhesion between enterocytes in short-term exposures to antioxidants and 1,2-dimethylhydrazine]. / Izmenenie stseplennosti mezhdu énterotsitami pri kratkovremennykh vozdeistviiakh antioksidantov i 1,2-dimetilgidrazina.

Ascorbic acid, alpha-tocopherol acetate, butilated hydroxytoluene, butilated hydroxyphenol, and sodium selenite have no influence on the intercellular adhesion in colon epithelium of mice. These antioxidants can drop or prevent from the increase in colonocyte adhesion induced by a single injection of colon carcinogen--1,2-dimethylhydrazine. With a simultaneous instillation of antioxidants and the colon carcinogen, the protective effect drops to zero in the following line: ascorbic acid--alpha-tocopherol acetate--butilated hydroxytoluene--sodium selenite--butilated hydroxyphenol. On instillation of the antioxidants 8-9 days after single injections of 1,2-dimethylhydrazine, the protective effect dropped to zero in the line: ascorbic acid--sodium selenite--alpha-tocopherol acetate--butilated hydroxytoluene. The data obtained give rise to a conclusion that the investigated effects of antioxidants may correlate with their anticarcinogenic actions.

[Changes in the adhesiveness between enterocytes after short-term blastomogenic exposures]. / Izmenenie stseplennosti mezhdu énterotsitami posle kratkovremennykh blastomogennykh vozdeistvii.

Following short-term local applications of high doses of N-methyl-N-nitrozourea and 7,2-dimethylbenz(a)antracen, the intercellular adhesion in the distal colon epithelium of ice retains increased at least for a month. The magnitude of this shift and its duration ops both with moving away from the area of application, or with reducing the doses of carcinogens to be closely related to the frequency of tumour production in the site of epithelium under chronic local applications of N-methyl-N-nitrozourea. After the application of noncarcinogenic methylurea or the subcutaneous injection of 1,2-dimethylhydrazine to the mice resistant to its carcinogenic action the wavy fluctuations of the magnitude of intercellular adhesion disappear within a week. The following conclusion can be drawn from the results: the long-term increase in enterocyte-enterocyte adhesion may be an earlier sign of the colon epithelium reaction to carcinogenic action.

[Vitamin A prevents an increase in epitheliocyte adhesion induced by carcinogens in the epidermis of rats and the large intestine of mice]. / Vitamin A prepiatstvuet uvelicheniiu stsepleniia épiteliotsitov, indutsiruemomu kantserogenami v épidermise krys i tolstoi kishke myshei.

The data obtained suggest that high doses of vitamin A may prevent from the carcinogen-induced increase in adhesion between mature cells in the rat epidermis and murine colon.