[Indicators of prostaglandin synthase activity in thrombocytes of patients with schizophrenia with positive and negative disorders]. / Pokazateli aktivnosti prostaglandin-sintetazy trombotsitov u bol'nykh shizofreniei s pozitivnymi i negativnymi rasstroistvami.

A study was made of the activity of prostaglandin-synthetase in isolated platelets from the 2 groups of schizophrenic patients: with the predominance of positive (group I) and negative (group II) disorders. It has been demonstrated that the activity of prostaglandin-synthetase in isolated platelets from patients with hallucinatory delirium++ disorders is considerably higher (p less than 0.01) than the activity of prostaglandin-synthetase in isolated platelets from patients with the predominance of negative symptoms. The data obtained once more raise a question of the ++patho-chemical heterogeneity of schizophrenia, which also pertains to prostaglandins. The authors discuss a possibility of the relationship in schizophrenic patients between the regulatory system of prostaglandin synthesis and the central hypothalamohypophyseal mechanism by which homeostasis is regulated.

[Methodological approaches to evaluation of prostaglandin synthesis by isolated human thrombocytes]. / Metodicheskie podkhody pri otsenke obrazovaniia prostaglandinov izolirovannymi trombotsitami cheloveka.

Individual steps of prostaglandin-synthetase activity evaluation in human platelets are considered in detail, involving isolation of platelets, incubation of washed cells with labelled arachidonic or dihomo-gamma-linolenic acids, extraction of prostaglandins from incubation medium and their separation as well as quantitative estimation of the prostaglandins developed (nmoles/10(9) platelets/10 min). The methodical approaches suggested enabled not only to avoid some errors during estimation of the prostaglandin-synthetase activity in individual platelets but also to increase accuracy, sensitivity and specificity of the procedure as compared with similar methods.

Is prostacyclin a major prostaglandin produced by endothelial cells in culture?

Prostaglandin biosynthetic activity of cultured human aortic and umbilical vein endothelial cells (passages 3-9) and of human aortic subendothelial cells (passage 0) was studied. Labelled arachidonic acid or endoperoxide H2 (final concentrations, 10 microM and 3.5 microM, respectively) were used as prostaglandin synthesis precursors. Arachidonic acid metabolites released into the incubation medium were separated by thin-layer chromatography and assayed for radioactivity. It has been demonstrated that endothelial and subendothelial cells in culture synthesize, besides prostacyclin, significant quantities of other prostaglandins, such as PGF2, PGE2, as well as thromboxane B2.

Regression of atherosclerotic manifestations in primary culture of human aortic cells: effects of prostaglandins.

The effect of different prostaglandins on cell proliferation and intracellular lipid content in primary culture of human aortic cells has been studied. It was demonstrated that prostacyclin, its stable analogues (carbacyclin and 6 beta-PGI1), and prostaglandins E1, E2, D2 taken in the concentration of 0.5 micrograms/ml and 10 micrograms/ml decreased the 3H-thymidine uptake into cultured intimal smooth muscle cells by 2-3-fold. Carbacyclin and 6 beta-PGI1 also lowered by 1.5-2-fold the triglyceride and cholesteryl ester levels in cells cultured from atherosclerotic lesions. Prostaglandins E1, E2, D2 in the concentration of 10 micrograms/ml decreased by 20-40% total cholesterol level in cultured cells.

Significance of myocardial prostaglandin biosynthesis and the influence of mechanical loading, endogenous mediators and cardiovascular drugs.

Isolated perfused and electrically driven heart preparations of guinea pigs and tissue from different parts of the rabbit hearts have the capacity to rapidly synthesize prostacyclin (PGI2) and thromboxane (TXB2). Auricles showed a higher PGI2 formation than ventricles. Addition of arachidonic acid or PGH2 markedly enhanced the myocardial PGI2 biosynthesis. After acute pressure overload by a graduated aortic stenosis the PGI2 and TXB2 formation of the myocardium is decreased possibly caused by a diminished availability of substrate, an alteration of enzyme activities or changes in the functional state of the cardiac tissue. Pretreatment with dipyridamole or propranolol again induced an increase of this diminished PGI2 and TXB2 synthesis. The PGI2 formation of electrically driven ventricular strips enhanced with an increased stimulation rate. Ouabain, antianginal drugs (dipyridamole, oxyfedrine, propranolol) and endogenous mediators (norepinephrine, histamine, adenosine) induced a significant rise of the cardiac PGI2 formation. The results suggest that the cardiac prostaglandin biosynthesis is involved in the action of the myocardium indicating heart sufficiency and an adaptability to mechanical loading or drug influence.

Prostacyclin formation by human aorta in different types of atherosclerotic lesion.

Human aortic samples were taken from uninvolved areas, fatty streaks and atherosclerotic plaques within 3 hrs after sudden death. Prostacyclin formed after 3-min incubation was estimated by ADP-induced platelet aggregation inhibitory method and by radioimmunoassay as 6-keto prostaglandin FI alpha. Atherosclerotic plaques exhibited a strong decrease in their capacity to synthesize prostacyclin. In comparison with normal there was not significant difference in the prostacyclin releasing value from the fatty streaks while individual samples had considerable variety.

[Synthesis and anti-aggregating activity of 11-deoxyprostacyclin]. / Sintez i antiagregatsionnaia aktivnost' 11=dezoksiprostatsiklina.

11-Deoxyprostacyclin was prepared in three stages starting from the 11-deoxyprostaglandin F2 alpha methyl ester. 11-Deoxyanalog showed 0,9% of natural prostacyclin potency in inhibition of platelet aggregation.

[Effect of trapidil on prostacyclin formation by rabbit heart tissue]. / Vliianie trapidila na obrazovanie prostatsiklina tkan'iu serdtsa krolika.

The release of prostacycline-like compound (PGI2) from the rabbit myocardium was estimated from its ability to inhibit platelet aggregation. Pieces of cardiac tissue were incubated in 0.05% M Tris buffer (pH 8) with arachidonic acid for 10 minutes. The aliquot of incubation medium was added to the rabbit platelet-rich plasma, and PGI2 generation was estimated from the ADP-induced aggregation as compared with antiaggregation activity produced by a known amount of synthetic PGI2. Trapidil (0.7 mM) increased PGI2 generation in the rabbit myocardium from 0.22 +/- 0.03 to 0.41 +/- 0.07 ng/mg wet weight of tissue (n = 7), p less than 0.01), but had no influence on the radioimmunologically assayed content of prostaglandins E and F2 in the incubation medium. Activation effect of trapidil on PGI2 generation in the rat aorta (Kawamura et al, 1980) and rabbit heart (our data), and its inhibitory effect both on the biosynthesis and thromboxan A2 action (Ohnishi et al, 1981) suggest that antiaggregation and coronarolytic actions, positive inotropic and chronotropic effects of trapidil on the myocardium are mediated via local generation of PGI2 and thromboxan A2.

[Determination of prostacyclin biosynthesis in biological specimens by the inhibition of thrombocyte aggregation]. / Opredelenie biosinteza prostatsiklina v biologicheskikh obraztsakh metodom ingibirovaniia agregatsii trombotsitov.

The method of platelet aggregation inhibition was used for determination of prostacycline-like activity (PGI2) in the process of incubation of biological samples with arachidonic acid. The choice of optimal conditions to carry out the experiment allowed the authors to estimate the level of PGI2 formation in pieces of cardiac tissue (left and right ventricle, left and right auricles), kidneys (internal and external layers), thoracic aorta. Application of the method to investigate the selective effect on PGI2 biosynthesis in vitro will promote the development of new approaches to prevention and treatment of some cardiovascular diseases.

[Relationship between myocardial contractile activity and the concentration of endogenous prostaglandins in the heart]. / Zavisimost' mezhdu sokratitel'noi aktivnost'iu miokarda i soderzhaniem v serdtse éndogennykh prostaglandinov.

The time-dependent positive correlation between myocardial contractility and myocardial level of prostaglandins (PG) was found after acute pressure overload. The PG level and contractility were observed to correlate well just after aortal stenosis. This correlation became less marked after more prolonged periods of adaptation to overload. A suggestion is made that a rapid increase in the PG content is required for triggering the biochemical mechanism of heart adaptation after the stressful factor.

Heart adaptation to acute pressure overload: an involvement of endogenous prostaglandins.

The purpose of this investigation was to study the relationships between the contractile behavior of the heart and myocardial prostaglandins. Using an open-chest model in rabbits, we assayed the left ventricular tissue content to prostaglandins (PG) E and F2 alpha at various intervals following acute pressure overload created by graduated aortic stenosis. The results suggest that the rabbits could be divided into two distinct groups based on specific hemodynamic changes following coarctation (systolic and diastolic pressure, dP/dt, and contractility index). The first group included rabbits whose adaptation to pressure overload was expressed as a gradual increase in the contractility index. The second group was comprised of rabbits that developed heart failure following coarctation. The increase in contractility in response to overload in the first group was paralleled by an increase in the content of PGE and PGF 2 alpha in the left ventricle, whereas, in rabbits with heart failure, the prostaglandin level did not rise above that of the control hearts. It is suggested that an increased endogenous prostaglandin content may be an important factor in adaptation to acute overload.